chr1-10474995-C-G

Position:

chr1-10474995-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_004565.3(PEX14):c.29C>G(p.Pro10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,610,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00074 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000070 ( 0 hom. )

Consequence

PEX14
NM_004565.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 2.98

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0072695613).

BP6

Variant 1-10474995-C-G is Benign according to our data. Variant chr1-10474995-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 593805.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX14	NM_004565.3 linkuse as main transcript	c.29C>G	p.Pro10Arg	missense_variant	1/9	ENST00000356607.9	NP_004556.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX14	ENST00000356607.9 linkuse as main transcript	c.29C>G	p.Pro10Arg	missense_variant	1/9	1	NM_004565.3	ENSP00000349016	P1	O75381-1
PEX14	ENST00000491661.2 linkuse as main transcript	c.14C>G	p.Pro5Arg	missense_variant	1/6	2		ENSP00000465473
PEX14	ENST00000472851.1 linkuse as main transcript	n.293+2415C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000742

AC:

113

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000167

AC:

AN:

239350

Hom.:

AF XY:

0.000108

AC XY:

AN XY:

130148

show subpopulations

Gnomad AFR exome

AF:

0.00256

Gnomad AMR exome

AF:

0.0000297

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000928

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000700

AC:

102

AN:

1457834

Hom.:

Cov.:

AF XY:

0.0000648

AC XY:

AN XY:

724824

show subpopulations

Gnomad4 AFR exome

AF:

0.00266

Gnomad4 AMR exome

AF:

0.0000905

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000997

GnomAD4 genome

AF:

0.000742

AC:

113

AN:

152332

Hom.:

Cov.:

AF XY:

0.000671

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00272

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000793

Hom.:

Bravo

AF:

0.000771

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000165

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Aug 24, 2017

- -

Peroxisome biogenesis disorder, complementation group K

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 08, 2024

- -

PEX14-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 31, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.37

T;T

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.0073

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.055

Sift

Uncertain

0.014

D;.

Sift4G

Uncertain

0.026

D;T

Polyphen

0.87

P;.

Vest4

0.38

MVP

0.20

MPC

0.45

ClinPred

0.082

GERP RS

4.8

Varity_R

0.32

gMVP

0.37

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