1-10629867-C-T

Variant names:

• chr1-10629867-C-T
• rs2128414
• NM_004565.3:c.1014C>T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004565.3(PEX14):​c.1014C>T​(p.Asp338Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 1,611,834 control chromosomes in the GnomAD database, including 2,504 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (242 hom., cov: 32)
  • Exomes 𝑓: 0.046 (2262 hom.)
• Consequence: PEX14 NM_004565.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.0630

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 1-10629867-C-T is Benign according to our data. Variant chr1-10629867-C-T is described in ClinVar as [Benign]. Clinvar id is 167453.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.063 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX14	NM_004565.3	c.1014C>T	p.Asp338Asp	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.1014C>T	p.Asp338Asp	synonymous_variant	Exon 9 of 9	1	NM_004565.3	ENSP00000349016.4

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 7178 AN: 151690 Hom.: 243 Cov.: 32

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0338

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0425

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0344

Gnomad OTH AF: 0.0480

GnomAD3 exomes AF: 0.0568 AC: 14144 AN: 248906 Hom.: 646 AF XY: 0.0599 AC XY: 8082 AN XY: 134884

Gnomad AFR exome AF: 0.0572

Gnomad AMR exome AF: 0.0303

Gnomad ASJ exome AF: 0.0310

Gnomad EAS exome AF: 0.119

Gnomad SAS exome AF: 0.140

Gnomad FIN exome AF: 0.0461

Gnomad NFE exome AF: 0.0368

Gnomad OTH exome AF: 0.0497

GnomAD4 exome AF: 0.0455 AC: 66439 AN: 1460026 Hom.: 2262 Cov.: 31 AF XY: 0.0480 AC XY: 34845 AN XY: 726306

Gnomad4 AFR exome AF: 0.0551

Gnomad4 AMR exome AF: 0.0325

Gnomad4 ASJ exome AF: 0.0298

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.132

Gnomad4 FIN exome AF: 0.0493

Gnomad4 NFE exome AF: 0.0359

Gnomad4 OTH exome AF: 0.0554

GnomAD4 genome AF: 0.0473 AC: 7174 AN: 151808 Hom.: 242 Cov.: 32 AF XY: 0.0479 AC XY: 3552 AN XY: 74178

Gnomad4 AFR AF: 0.0552

Gnomad4 AMR AF: 0.0338

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.126

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.0425

Gnomad4 NFE AF: 0.0343

Gnomad4 OTH AF: 0.0475

Alfa AF: 0.0381 Hom.: 51

Bravo AF: 0.0458

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Sep 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 16, 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

Dec 18, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

- -

Peroxisome biogenesis disorder 13A (Zellweger) Benign:1

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.6
DANN	Benign	0.62
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8

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

Other links and lift over

dbSNP: rs2128414; hg19: chr1-10689924; COSMIC: COSV63062147;