1-10629885-G-T

Variant names:

• chr1-10629885-G-T
• rs11539794
• NM_004565.3:c.1032G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004565.3(PEX14):​c.1032G>T​(p.Gly344Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,612,824 control chromosomes in the GnomAD database, including 25,665 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G344G) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.13 (1740 hom., cov: 31)
  • Exomes 𝑓: 0.18 (23925 hom.)
• Consequence: PEX14 NM_004565.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.183
• Publications: 11 publications found

Genes affected

PEX14 (HGNC:8856): (peroxisomal biogenesis factor 14) This gene encodes an essential component of the peroxisomal import machinery. The protein is integrated into peroxisome membranes with its C-terminus exposed to the cytosol, and interacts with the cytosolic receptor for proteins containing a PTS1 peroxisomal targeting signal. The protein also functions as a transcriptional corepressor and interacts with a histone deacetylase. A mutation in this gene results in one form of Zellweger syndrome. [provided by RefSeq, Jul 2008]

PEX14 Gene-Disease associations (from GenCC):

• peroxisome biogenesis disorder

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• peroxisome biogenesis disorder 13A (Zellweger)

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Zellweger spectrum disorders

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 1-10629885-G-T is Benign according to our data. Variant chr1-10629885-G-T is described in ClinVar as Benign. ClinVar VariationId is 167454.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX14	NM_004565.3	c.1032G>T	p.Gly344Gly	synonymous_variant	Exon 9 of 9	ENST00000356607.9	NP_004556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX14	ENST00000356607.9	c.1032G>T	p.Gly344Gly	synonymous_variant	Exon 9 of 9	1	NM_004565.3	ENSP00000349016.4

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20464 AN: 151780 Hom.: 1740 Cov.: 31

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.0236

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.193

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.149

GnomAD2 exomes AF: 0.154 AC: 38361 AN: 249532 AF XY: 0.162

Gnomad AFR exome AF: 0.0389

Gnomad AMR exome AF: 0.0884

Gnomad ASJ exome AF: 0.203

Gnomad EAS exome AF: 0.0173

Gnomad FIN exome AF: 0.188

Gnomad NFE exome AF: 0.188

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.177 AC: 258579 AN: 1460924 Hom.: 23925 Cov.: 33 AF XY: 0.178 AC XY: 129462 AN XY: 726760

African (AFR) AF: 0.0373 AC: 1250 AN: 33472

American (AMR) AF: 0.0934 AC: 4172 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 5353 AN: 26112

East Asian (EAS) AF: 0.0368 AC: 1459 AN: 39682

South Asian (SAS) AF: 0.199 AC: 17172 AN: 86180

European-Finnish (FIN) AF: 0.186 AC: 9931 AN: 53288

Middle Eastern (MID) AF: 0.226 AC: 1298 AN: 5740

European-Non Finnish (NFE) AF: 0.187 AC: 207524 AN: 1111420

Other (OTH) AF: 0.173 AC: 10420 AN: 60354

GnomAD4 genome AF: 0.135 AC: 20465 AN: 151900 Hom.: 1740 Cov.: 31 AF XY: 0.135 AC XY: 10047 AN XY: 74218

African (AFR) AF: 0.0427 AC: 1771 AN: 41438

American (AMR) AF: 0.116 AC: 1776 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 692 AN: 3470

East Asian (EAS) AF: 0.0239 AC: 123 AN: 5154

South Asian (SAS) AF: 0.179 AC: 863 AN: 4808

European-Finnish (FIN) AF: 0.193 AC: 2042 AN: 10572

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12663 AN: 67890

Other (OTH) AF: 0.147 AC: 309 AN: 2102

Alfa AF: 0.163 Hom.: 1057

Bravo AF: 0.126

Asia WGS AF: 0.103 AC: 356 AN: 3474

EpiCase AF: 0.192

EpiControl AF: 0.192

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

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. -

Dec 15, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 01, 2014

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Peroxisome biogenesis disorder 13A (Zellweger) Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

Peroxisome biogenesis disorder, complementation group K Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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	-0.57
CADD	Benign	5.3
DANN	Benign	0.68
PhyloP100		0.18
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.9
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11539794; hg19: chr1-10689942; COSMIC: COSV108172663;