7-92501975-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000466.3(PEX1):c.2331C>A(p.Gly777Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.919 in 1,613,548 control chromosomes in the GnomAD database, including 681,914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.93 ( 65997 hom., cov: 32)

Exomes 𝑓: 0.92 ( 615917 hom. )

Consequence

PEX1
NM_000466.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:17

Conservation

PhyloP100: 2.52

Variant links:

Genes affected

PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

PEX1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 7-92501975-G-T is Benign according to our data. Variant chr7-92501975-G-T is described in ClinVar as [Benign]. Clinvar id is 93105.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-92501975-G-T is described in Lovd as [Benign]. Variant chr7-92501975-G-T is described in Lovd as [Pathogenic].

BP7

Synonymous conserved (PhyloP=2.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.968 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX1	NM_000466.3 link	c.2331C>A	p.Gly777Gly	synonymous_variant	Exon 14 of 24	ENST00000248633.9	NP_000457.1	O43933-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX1	ENST00000248633.9 link	c.2331C>A	p.Gly777Gly	synonymous_variant	Exon 14 of 24	1	NM_000466.3	ENSP00000248633.4		O43933-1

Frequencies

GnomAD3 genomes

AF:

0.930

AC:

141562

AN:

152186

Hom.:

65939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.976

Gnomad AMI

AF:

0.933

Gnomad AMR

AF:

0.944

Gnomad ASJ

AF:

0.906

Gnomad EAS

AF:

0.967

Gnomad SAS

AF:

0.935

Gnomad FIN

AF:

0.871

Gnomad MID

AF:

0.946

Gnomad NFE

AF:

0.907

Gnomad OTH

AF:

0.913

GnomAD3 exomes

AF:

0.921

AC:

231601

AN:

251340

Hom.:

106854

AF XY:

0.920

AC XY:

124972

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.976

Gnomad AMR exome

AF:

0.940

Gnomad ASJ exome

AF:

0.907

Gnomad EAS exome

AF:

0.968

Gnomad SAS exome

AF:

0.925

Gnomad FIN exome

AF:

0.866

Gnomad NFE exome

AF:

0.912

Gnomad OTH exome

AF:

0.913

GnomAD4 exome

AF:

0.918

AC:

1341151

AN:

1461244

Hom.:

615917

Cov.:

AF XY:

0.918

AC XY:

667282

AN XY:

726982

show subpopulations

Gnomad4 AFR exome

AF:

0.977

Gnomad4 AMR exome

AF:

0.940

Gnomad4 ASJ exome

AF:

0.908

Gnomad4 EAS exome

AF:

0.964

Gnomad4 SAS exome

AF:

0.926

Gnomad4 FIN exome

AF:

0.870

Gnomad4 NFE exome

AF:

0.915

Gnomad4 OTH exome

AF:

0.921

GnomAD4 genome

AF:

0.930

AC:

141681

AN:

152304

Hom.:

65997

Cov.:

AF XY:

0.929

AC XY:

69202

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.976

Gnomad4 AMR

AF:

0.944

Gnomad4 ASJ

AF:

0.906

Gnomad4 EAS

AF:

0.967

Gnomad4 SAS

AF:

0.936

Gnomad4 FIN

AF:

0.871

Gnomad4 NFE

AF:

0.907

Gnomad4 OTH

AF:

0.914

Alfa

AF:

0.919

Hom.:

36231

Bravo

AF:

0.938

Asia WGS

AF:

0.943

AC:

3279

AN:

3476

EpiCase

AF:

0.911

EpiControl

AF:

0.913

ClinVar

Significance: Benign

Submissions summary: Benign:17

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:8

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 29, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 92% of total chromosomes in ExAC -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 21, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jun 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Zellweger spectrum disorders

Benign:2

Mar 29, 2017

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Peroxisome biogenesis disorder 1A (Zellweger)

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 01, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Heimler syndrome 1

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Peroxisome biogenesis disorder 1B

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

7.0

DANN

Benign

0.68

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