1-10629867-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.0630

Publications

9 publications found

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 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

PEX14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 link	c.1014C>T	p.Asp338Asp	synonymous_variant	Exon 9 of 9	ENST00000356607.9	NP_004556.1	O75381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PEX14	ENST00000356607.9 link	c.1014C>T	p.Asp338Asp	synonymous_variant	Exon 9 of 9	1	NM_004565.3	ENSP00000349016.4		O75381-1

Frequencies

GnomAD3 genomes

AF:

0.0473

AC:

7178

AN:

151690

Hom.:

243

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0568

AC:

14144

AN:

248906

AF XY:

0.0599

show subpopulations

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 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.:

AF XY:

0.0480

AC XY:

34845

AN XY:

726306

show subpopulations

African (AFR)

AF:

0.0551

AC:

1843

AN:

33456

American (AMR)

AF:

0.0325

AC:

1450

AN:

44600

Ashkenazi Jewish (ASJ)

AF:

0.0298

AC:

777

AN:

26102

East Asian (EAS)

AF:

0.124

AC:

4927

AN:

39674

South Asian (SAS)

AF:

0.132

AC:

11344

AN:

86118

European-Finnish (FIN)

AF:

0.0493

AC:

2626

AN:

53298

Middle Eastern (MID)

AF:

0.0537

AC:

309

AN:

5758

European-Non Finnish (NFE)

AF:

0.0359

AC:

39823

AN:

1110688

Other (OTH)

AF:

0.0554

AC:

3340

AN:

60332

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

3399

6798

10196

13595

16994

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1688

3376

5064

6752

8440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0473

AC:

7174

AN:

151808

Hom.:

242

Cov.:

AF XY:

0.0479

AC XY:

3552

AN XY:

74178

show subpopulations

African (AFR)

AF:

0.0552

AC:

2285

AN:

41366

American (AMR)

AF:

0.0338

AC:

516

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.0271

AC:

AN:

3468

East Asian (EAS)

AF:

0.126

AC:

648

AN:

5124

South Asian (SAS)

AF:

0.149

AC:

713

AN:

4792

European-Finnish (FIN)

AF:

0.0425

AC:

449

AN:

10568

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0343

AC:

2332

AN:

67908

Other (OTH)

AF:

0.0475

AC:

100

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

321

642

963

1284

1605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0381

Hom.:

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

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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

- -

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

(source)

DANN

Benign

0.62

PhyloP100

-0.063

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over