NM_004565.3:c.384+14A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004565.3(PEX14):c.384+14A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,599,916 control chromosomes in the GnomAD database, including 18,358 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3289 hom., cov: 33)

Exomes 𝑓: 0.14 ( 15069 hom. )

Consequence

PEX14
NM_004565.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.520

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-10618431-A-T is Benign according to our data. Variant chr1-10618431-A-T is described in ClinVar as [Benign]. Clinvar id is 95145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PEX14	NM_004565.3 link	c.384+14A>T		intron_variant	Intron 5 of 8	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.384+14A>T		intron_variant	Intron 5 of 8	1	NM_004565.3	ENSP00000349016.4		O75381-1
PEX14	ENST00000491661.2 link	c.369+14A>T		intron_variant	Intron 5 of 5	2		ENSP00000465473.1		K7EK59

Frequencies

GnomAD3 genomes

AF:

0.190

AC:

28931

AN:

152152

Hom.:

3269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.182

Gnomad AMR

AF:

0.145

Gnomad ASJ

AF:

0.191

Gnomad EAS

AF:

0.0778

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.245

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.155

AC:

38508

AN:

248840

AF XY:

0.157

show subpopulations

Gnomad AFR exome

AF:

0.311

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.187

Gnomad EAS exome

AF:

0.0889

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.151

GnomAD4 exome

AF:

0.137

AC:

198517

AN:

1447646

Hom.:

15069

Cov.:

AF XY:

0.139

AC XY:

100463

AN XY:

721146

show subpopulations

African (AFR)

AF:

0.323

AC:

10690

AN:

33134

American (AMR)

AF:

0.109

AC:

4885

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

4799

AN:

26068

East Asian (EAS)

AF:

0.0726

AC:

2879

AN:

39630

South Asian (SAS)

AF:

0.195

AC:

16806

AN:

86018

European-Finnish (FIN)

AF:

0.233

AC:

12095

AN:

51936

Middle Eastern (MID)

AF:

0.168

AC:

967

AN:

5750

European-Non Finnish (NFE)

AF:

0.124

AC:

136480

AN:

1100456

Other (OTH)

AF:

0.149

AC:

8916

AN:

59974

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

8092

16184

24277

32369

40461

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.190

AC:

28992

AN:

152270

Hom.:

3289

Cov.:

AF XY:

0.196

AC XY:

14596

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.308

AC:

12820

AN:

41566

American (AMR)

AF:

0.146

AC:

2237

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

664

AN:

3468

East Asian (EAS)

AF:

0.0778

AC:

403

AN:

5182

South Asian (SAS)

AF:

0.186

AC:

899

AN:

4830

European-Finnish (FIN)

AF:

0.245

AC:

2597

AN:

10600

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.129

AC:

8777

AN:

68000

Other (OTH)

AF:

0.177

AC:

373

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1207

2415

3622

4830

6037

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.158

Hom.:

407

Bravo

AF:

0.185

Asia WGS

AF:

0.129

AC:

452

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 26, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Oct 26, 2015

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not specified

Benign:2

Apr 30, 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 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.14

(source)

DANN

Benign

0.56

PhyloP100

-0.52

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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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NM_004565.3:c.384+14A>T

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