chr1-10629885-G-T

Position:

chr1-10629885-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.183

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
PEX14	NM_004565.3 linkuse as main transcript	c.1032G>T	p.Gly344Gly	synonymous_variant	9/9	ENST00000356607.9	NP_004556.1	O75381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX14	ENST00000356607.9 linkuse as main transcript	c.1032G>T	p.Gly344Gly	synonymous_variant	9/9	1	NM_004565.3	ENSP00000349016.4		O75381-1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20464

AN:

151780

Hom.:

1740

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.154

AC:

38361

AN:

249532

Hom.:

3517

AF XY:

0.162

AC XY:

21906

AN XY:

135182

show subpopulations

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 SAS exome

AF:

0.196

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.:

AF XY:

0.178

AC XY:

129462

AN XY:

726760

show subpopulations

Gnomad4 AFR exome

AF:

0.0373

Gnomad4 AMR exome

AF:

0.0934

Gnomad4 ASJ exome

AF:

0.205

Gnomad4 EAS exome

AF:

0.0368

Gnomad4 SAS exome

AF:

0.199

Gnomad4 FIN exome

AF:

0.186

Gnomad4 NFE exome

AF:

0.187

Gnomad4 OTH exome

AF:

0.173

GnomAD4 genome

AF:

0.135

AC:

20465

AN:

151900

Hom.:

1740

Cov.:

AF XY:

0.135

AC XY:

10047

AN XY:

74218

show subpopulations

Gnomad4 AFR

AF:

0.0427

Gnomad4 AMR

AF:

0.116

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.0239

Gnomad4 SAS

AF:

0.179

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.187

Gnomad4 OTH

AF:

0.147

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

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, no assertion criteria provided	clinical testing	Mayo Clinic Laboratories, Mayo Clinic	Dec 15, 2015	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 13, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 01, 2014	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Peroxisome biogenesis disorder 13A (Zellweger)

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.3

DANN

Benign

0.68

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.9

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