Variant rs62509021 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP7BA1

This summary comes from the ClinGen Evidence Repository: The c.1316-35C>T variant in PAH has a MAF of 0.02321 in the gnomAD European (Non-Finnish) population. This intronic variant does not have a predicted impact on splicing. In summary this variant meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BA1, BP7 LINK:https://erepo.genome.network/evrepo/ui/classification/CA229433/MONDO:0009861/006

Frequency

Genomes: 𝑓 0.017 ( 34 hom., cov: 33)

Exomes 𝑓: 0.022 ( 444 hom. )

Consequence

PAH
NM_000277.3 intron

Scores

Clinical Significance

Benign reviewed by expert panel B:3O:1

Conservation

PhyloP100: -1.87

Variant links:

Genes affected

PAH (HGNC:8582): (phenylalanine hydroxylase) This gene encodes a member of the biopterin-dependent aromatic amino acid hydroxylase protein family. The encoded phenylalanine hydroxylase enzyme hydroxylates phenylalanine to tyrosine and is the rate-limiting step in phenylalanine catabolism. Deficiency of this enzyme activity results in the autosomal recessive disorder phenylketonuria. [provided by RefSeq, Aug 2017]

PAH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP7

BA1

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PAH	NM_000277.3 linkuse as main transcript	c.1316-35C>T		intron_variant		ENST00000553106.6
PAH	NM_001354304.2 linkuse as main transcript	c.1316-35C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PAH	ENST00000553106.6 linkuse as main transcript	c.1316-35C>T		intron_variant		1	NM_000277.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0167

AC:

2543

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00461

Gnomad AMI

AF:

0.0197

Gnomad AMR

AF:

0.0207

Gnomad ASJ

AF:

0.0190

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0161

AC:

4031

AN:

250524

Hom.:

AF XY:

0.0168

AC XY:

2283

AN XY:

135492

show subpopulations

Gnomad AFR exome

AF:

0.00329

Gnomad AMR exome

AF:

0.0130

Gnomad ASJ exome

AF:

0.0189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0139

Gnomad FIN exome

AF:

0.00977

Gnomad NFE exome

AF:

0.0229

Gnomad OTH exome

AF:

0.0182

GnomAD4 exome

AF:

0.0223

AC:

32486

AN:

1455256

Hom.:

444

Cov.:

AF XY:

0.0222

AC XY:

16076

AN XY:

724472

show subpopulations

Gnomad4 AFR exome

AF:

0.00354

Gnomad4 AMR exome

AF:

0.0145

Gnomad4 ASJ exome

AF:

0.0160

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0136

Gnomad4 FIN exome

AF:

0.00974

Gnomad4 NFE exome

AF:

0.0254

Gnomad4 OTH exome

AF:

0.0232

GnomAD4 genome

AF:

0.0167

AC:

2542

AN:

152286

Hom.:

Cov.:

AF XY:

0.0156

AC XY:

1163

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00460

Gnomad4 AMR

AF:

0.0207

Gnomad4 ASJ

AF:

0.0190

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.0126

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0218

Hom.:

Bravo

AF:

0.0165

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:1Other:1

not provided, no classification provided	literature only	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Phenylketonuria

Benign:1

Benign, reviewed by expert panel

curation

ClinGen PAH Variant Curation Expert Panel

Mar 27, 2020

The c.1316-35C>T variant in PAH has a MAF of 0.02321 in the gnomAD European (Non-Finnish) population. This intronic variant does not have a predicted impact on splicing. In summary this variant meets criteria to be classified as benign. PAH-specific ACMG/AMP criteria applied: BA1, BP7 -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.046

DANN

Benign

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over