Pubvar

12:103306579:C/T

GRCh37/hg19 position	12:103306579
GRCh38/hg38 position	12:102912801
Alleles (ref/alt)	C/T
dbSNP rsid	rs118092776
Gene symbol	PAH
Most severe consequence	missense_variant
Flanking sequence	AAACATGATTGTAGCACTGACCTCAAATAAG[C/T]GCAATACTTTGGCCAATGCACCAACTTCTTC
HGVS	NM_000277.3:c.158G>A NM_001354304.2:c.158G>A NP_000268.1:p.Arg53His NP_001341233.1:p.Arg53His More...

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Gene annotations

Transcript

Gene

Exon number

Consequence

HGVS cDNA

HGVS protein

Location

Protein location

NM_000277.3

PAH

missense_variant

c.158G>A

p.Arg53His

Exon 2

NM_001354304.2

PAH

missense_variant

c.158G>A

p.Arg53His

Exon 3

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Population frequency

Select populations: ALL LWK MKK YRI EUR FIN NFE CEU ASJ TSI EAS SAS CHB HAN CHD JPT AFR AMR ASW GIH MEX OTH

Database	Population	AC	AN	Hom	AF
1000 genomes	ALL	15	5008	-	0.00299521
	EUR	-	-	-	0.002
	EAS	-	-	-	0.0119
	SAS	-	-	-	0.001
	AFR	-	-	-	0
	AMR	-	-	-	0
ExAC	ALL	212	121382	1	0.001747
	FIN	1	6610	0	0.000151
	NFE	45	66726	0	0.000674
	EAS	138	8648	1	0.015957
	SAS	22	16508	0	0.001333
	AFR	1	10404	0	0.000096
	AMR	4	11578	0	0.000345
	OTH	1	908	0	0.001101
gnomAD genomes	ALL	34	30968	0	0.00109791
	FIN	1	3492	0	0.000286369
	NFE	9	15006	0	0.00059976
	ASJ	0	302	0	0
	EAS	21	1620	0	0.012963
	AFR	2	8728	0	0.000229148
	AMR	0	838	0	0
	OTH	1	982	0	0.00101833
gnomAD exomes	ALL	410	246138	3	0.00166573
	FIN	2	22274	0	8.97908e-05
	NFE	77	111620	0	0.000689841
	ASJ	2	9848	0	0.000203087
	EAS	244	17248	3	0.0141466
	SAS	45	30780	0	0.00146199
	AFR	1	15304	0	6.53424e-05
	AMR	31	33580	0	0.000923169
	OTH	8	5484	0	0.00145879
CONVERGE	ALL	-	-	-	0.017
HRC	ALL	46	64976	-	0.000707954

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Functional predictions

Tool	Score	Prediction
SIFT	0.053	tolerated
Polyphen2 HDIV	0.882	possibly damaging
Polyphen2 HVAR	0.305	benign
LRT	0.000008	deleterious
MutationTaster	0.999993	disease_causing
MutationAssessor	2.22	medium
FATHMM	-5.54	damaging
MetaSVM	0.7392	damaging
MetaLR	0.9016	damaging
PROVEAN	-2.76	damaging
CADD	2.933166	-
REVEL	0.789	-

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View on UCSC genome browser

Conservation

Conservation scores are retrieved from UCSC genome browser. The conservation levels are defined by simple cutoff values. If the conservation levels do not agree with each other, you can manually check whether this variant is conserved with UCSC genome browser.

Method	Score	Level
GERP++	5.46	Conserved
phastCons46way primates	0.922	Highly conserved
phastCons46way placental	1.000	Highly conserved
phastCons100way vertebrates	1.000	Highly conserved
phyloP46way primates	0.655	Conserved
phyloP46way placental	2.549	Conserved
phyloP100way vertebrates	3.178	Not conserved

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ClinVar

Accession	Clinical significance	Date last evaluated	Review status	Method	Disease name	Disease symbol	Disease inheritance	Pubmed
RCV000088842	Uncertain significance	2020-04-30	criteria provided, single submitter	literature only	not provided	-	-	-
RCV000490373	Uncertain significance	2018-08-10	reviewed by expert panel	clinical testing	Phenylketonuria	PKU	Autosomal recessive inheritance	12655553 9452061 28492532 15503242 16256386 19915519 18294361 16253218 25741868 24401910
RCV001175359	Benign	2022-02-24	criteria provided, single submitter	clinical testing	not specified	-	-	32893076 29653233 9452061 31355225 33465300 30904546 30887117 30838026 30747360 33803550 24401910 26666653 29032371 31332730 26322415

Accession

Clinical significance

Date last evaluated

Review status

Method

Disease name

Disease symbol

Disease inheritance

Pubmed

RCV000088842

Uncertain significance

2020-04-30

criteria provided, single submitter

literature only

not provided

RCV000490373

Uncertain significance

2018-08-10

reviewed by expert panel

clinical testing

Phenylketonuria

PKU

Autosomal recessive inheritance

Benign

2022-02-24

criteria provided, single submitter

clinical testing

not specified

InterVar

InterVar is a software tool for clinical interpretation of genetic variants by the ACMG/AMP 2015 guideline. The eveidence tags that variant met are highlighted. Please note that evidence tags with need to be evaluated manually.

Class: Uncertain significance

	Benign		Pathogenic
	Strong	Supporting	Supporting	Moderate	Strong	Very Strong
Population data	BA1 BS1 BS2			PM2	PS4
Computational and predictive data		BP1 BP3 BP4 BP7	PP3	PM4 PM5	PS1	PVS1
Functional data	BS3		PP2	PM1	PS3
Segregation data	BS4		PP1	PP1	PP1
De novo data				PM6	PS2
Allelic data		BP2		PM3
Other database		BP6	PP5
Other data		BP5	PP4

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Amino acid change

The physichemical property of amino acid change.

Trait	Arg (R)	His (H)
Amino acid name	Arginine	Histidine
Side chain class	basic	basic aromatic
Polarity	basic polar	basic polar
Charge (pH=7.4)	positively charged	positively or neutrally charged
Hydropathy	hydrophilic	moderate
Molecular weight	174.203	155.156