Variant 12-102843690-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BA1BP7

This summary comes from the ClinGen Evidence Repository: This c.1155C>G (p.Leu385=) synonymous variant in PAH is not predicted to have a splice-altering consequence. This variant was present at a high frequency of 0.840256 in 1000 genomes and 0.858145 in ExAC. In summary, this variant meets criteria to be classified as a benign for PAH. PAH-specific ACMG/AMP criteria applied: BP7, BA1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA180265/MONDO:0009861/006

Frequency

Genomes: 𝑓 0.84 ( 53986 hom., cov: 29)

Exomes 𝑓: 0.85 ( 528935 hom. )

Consequence

PAH
NM_000277.3 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:7

Conservation

PhyloP100: -0.0970

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:

PAH (HGNC:):

PAH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP7

For more information check the summary or visit ClinGen Evidence Repository.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PAH	NM_000277.3 linkuse as main transcript	c.1155C>G	p.Leu385Leu	synonymous_variant	11/13	ENST00000553106.6	NP_000268.1	P00439A0A024RBG4
PAH	NM_001354304.2 linkuse as main transcript	c.1155C>G	p.Leu385Leu	synonymous_variant	12/14		NP_001341233.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PAH	ENST00000553106.6 linkuse as main transcript	c.1155C>G	p.Leu385Leu	synonymous_variant	11/13	1	NM_000277.3	ENSP00000448059.1		P00439

Frequencies

GnomAD3 genomes

AF:

0.842

AC:

127910

AN:

151868

Hom.:

53951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.804

Gnomad AMI

AF:

0.792

Gnomad AMR

AF:

0.885

Gnomad ASJ

AF:

0.820

Gnomad EAS

AF:

0.840

Gnomad SAS

AF:

0.872

Gnomad FIN

AF:

0.907

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.846

Gnomad OTH

AF:

0.844

GnomAD3 exomes

AF:

0.861

AC:

216427

AN:

251268

Hom.:

93489

AF XY:

0.860

AC XY:

116737

AN XY:

135782

show subpopulations

Gnomad AFR exome

AF:

0.799

Gnomad AMR exome

AF:

0.913

Gnomad ASJ exome

AF:

0.822

Gnomad EAS exome

AF:

0.839

Gnomad SAS exome

AF:

0.887

Gnomad FIN exome

AF:

0.907

Gnomad NFE exome

AF:

0.847

Gnomad OTH exome

AF:

0.851

GnomAD4 exome

AF:

0.851

AC:

1242694

AN:

1461134

Hom.:

528935

Cov.:

AF XY:

0.852

AC XY:

619004

AN XY:

726890

show subpopulations

Gnomad4 AFR exome

AF:

0.802

Gnomad4 AMR exome

AF:

0.908

Gnomad4 ASJ exome

AF:

0.823

Gnomad4 EAS exome

AF:

0.846

Gnomad4 SAS exome

AF:

0.889

Gnomad4 FIN exome

AF:

0.910

Gnomad4 NFE exome

AF:

0.845

Gnomad4 OTH exome

AF:

0.849

GnomAD4 genome

AF:

0.842

AC:

128004

AN:

151986

Hom.:

53986

Cov.:

AF XY:

0.847

AC XY:

62900

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.804

Gnomad4 AMR

AF:

0.885

Gnomad4 ASJ

AF:

0.820

Gnomad4 EAS

AF:

0.840

Gnomad4 SAS

AF:

0.872

Gnomad4 FIN

AF:

0.907

Gnomad4 NFE

AF:

0.846

Gnomad4 OTH

AF:

0.845

Alfa

AF:

0.839

Hom.:

13908

Bravo

AF:

0.837

EpiCase

AF:

0.834

EpiControl

AF:

0.837

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

Phenylketonuria

Benign:5

Benign, criteria provided, single submitter	clinical testing	Pars Genome Lab	Jul 01, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Nov 16, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, reviewed by expert panel	curation	ClinGen PAH Variant Curation Expert Panel	Dec 09, 2022	This c.1155C>G (p.Leu385=) synonymous variant in PAH is not predicted to have a splice-altering consequence. This variant was present at a high frequency of 0.840256 in 1000 genomes and 0.858145 in ExAC. In summary, this variant meets criteria to be classified as a benign for PAH. PAH-specific ACMG/AMP criteria applied: BP7, BA1. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

May 16, 2017

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.2

DANN

Benign

0.60

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