NM_004565.3:c.156C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004565.3(PEX14):c.156C>T(p.Phe52Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,596,574 control chromosomes in the GnomAD database, including 77,544 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.26 ( 5741 hom., cov: 31)

Exomes 𝑓: 0.31 ( 71803 hom. )

Consequence

PEX14
NM_004565.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.38

Publications

24 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 1-10536284-C-T is Benign according to our data. Variant chr1-10536284-C-T is described in ClinVar as [Benign]. Clinvar id is 259434.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX14	NM_004565.3 link	c.156C>T	p.Phe52Phe	synonymous_variant	Exon 3 of 9	ENST00000356607.9	NP_004556.1	O75381-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PEX14	ENST00000356607.9 link	c.156C>T	p.Phe52Phe	synonymous_variant	Exon 3 of 9	1	NM_004565.3	ENSP00000349016.4	O75381-1
PEX14	ENST00000491661.2 link	c.141C>T	p.Phe47Phe	synonymous_variant	Exon 3 of 6	2		ENSP00000465473.1	K7EK59
PEX14	ENST00000472851.1 link	n.517C>T		non_coding_transcript_exon_variant	Exon 4 of 4	3
PEX14	ENST00000492696.1 link	n.245C>T		non_coding_transcript_exon_variant	Exon 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.258

AC:

39120

AN:

151842

Hom.:

5742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.351

Gnomad AMR

AF:

0.338

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.208

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.338

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.322

Gnomad OTH

AF:

0.277

GnomAD2 exomes

AF:

0.295

AC:

74030

AN:

251160

AF XY:

0.291

show subpopulations

Gnomad AFR exome

AF:

0.101

Gnomad AMR exome

AF:

0.412

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.212

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.313

Gnomad OTH exome

AF:

0.293

GnomAD4 exome

AF:

0.310

AC:

447902

AN:

1444612

Hom.:

71803

Cov.:

AF XY:

0.307

AC XY:

221248

AN XY:

719704

show subpopulations

African (AFR)

AF:

0.0987

AC:

3280

AN:

33244

American (AMR)

AF:

0.403

AC:

18025

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.267

AC:

6938

AN:

26020

East Asian (EAS)

AF:

0.186

AC:

7391

AN:

39642

South Asian (SAS)

AF:

0.223

AC:

19142

AN:

85992

European-Finnish (FIN)

AF:

0.332

AC:

17737

AN:

53386

Middle Eastern (MID)

AF:

0.228

AC:

1306

AN:

5740

European-Non Finnish (NFE)

AF:

0.325

AC:

356349

AN:

1096072

Other (OTH)

AF:

0.297

AC:

17734

AN:

59810

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

13598

27196

40795

54393

67991

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11374

22748

34122

45496

56870

<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:

0.257

AC:

39111

AN:

151962

Hom.:

5741

Cov.:

AF XY:

0.258

AC XY:

19127

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.107

AC:

4448

AN:

41492

American (AMR)

AF:

0.337

AC:

5154

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.265

AC:

920

AN:

3470

East Asian (EAS)

AF:

0.208

AC:

1073

AN:

5152

South Asian (SAS)

AF:

0.239

AC:

1147

AN:

4808

European-Finnish (FIN)

AF:

0.338

AC:

3561

AN:

10526

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.322

AC:

21842

AN:

67926

Other (OTH)

AF:

0.275

AC:

580

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1411

2822

4232

5643

7054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

398

796

1194

1592

1990

<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:

0.297

Hom.:

7510

Bravo

AF:

0.253

Asia WGS

AF:

0.253

AC:

879

AN:

3478

EpiCase

AF:

0.314

EpiControl

AF:

0.318

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

- -

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. -

Oct 21, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

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. -

not specified

Benign:1

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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