Variant 7-92518145-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000466.3(PEX1):c.468A>C(p.Gln156His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000497 in 1,610,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. Q156Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

PEX1
NM_000466.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.86

Variant links:

Genes affected

PEX1 (HGNC:8850): (peroxisomal biogenesis factor 1) This gene encodes a member of the AAA ATPase family, a large group of ATPases associated with diverse cellular activities. This protein is cytoplasmic but is often anchored to a peroxisomal membrane where it forms a heteromeric complex and plays a role in the import of proteins into peroxisomes and peroxisome biogenesis. Mutations in this gene have been associated with complementation group 1 peroxisomal disorders such as neonatal adrenoleukodystrophy, infantile Refsum disease, and Zellweger syndrome. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2013]

PEX1 links:

PEX1 (HGNC:):

PEX1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2571693).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX1	NM_000466.3 linkuse as main transcript	c.468A>C	p.Gln156His	missense_variant	4/24	ENST00000248633.9	NP_000457.1	O43933-1
PEX1	NM_001282677.2 linkuse as main transcript	c.468A>C	p.Gln156His	missense_variant	4/23		NP_001269606.1	O43933A0A0C4DG33
PEX1	XM_047420472.1 linkuse as main transcript	c.468A>C	p.Gln156His	missense_variant	4/23		XP_047276428.1
PEX1	NM_001282678.2 linkuse as main transcript	c.-157A>C		5_prime_UTR_variant	4/24		NP_001269607.1	O43933B4DER6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PEX1	ENST00000248633.9 linkuse as main transcript	c.468A>C	p.Gln156His	missense_variant	4/24	1	NM_000466.3	ENSP00000248633.4	O43933-1
PEX1	ENST00000428214.5 linkuse as main transcript	c.468A>C	p.Gln156His	missense_variant	4/23	1		ENSP00000394413.1	A0A0C4DG33
PEX1	ENST00000438045.5 linkuse as main transcript	c.273+3957A>C		intron_variant		2		ENSP00000410438.1	O43933-2
PEX1	ENST00000484913.5 linkuse as main transcript	n.507A>C		non_coding_transcript_exon_variant	4/24	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000119

AC:

AN:

251388

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135862

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000480

AC:

AN:

1458772

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725986

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000541

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000250

Hom.:

Bravo

AF:

0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.18

CADD

Benign

2.3

DANN

Benign

0.92

DEOGEN2

Benign

0.093

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.81

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.26

T;T

MetaSVM

Uncertain

0.48

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.2

N;N

REVEL

Uncertain

0.46

Sift

Uncertain

0.015

D;D

Sift4G

Uncertain

0.057

T;D

Polyphen

0.94

P;.

Vest4

0.45

MutPred

0.56

Loss of stability (P = 0.1459);Loss of stability (P = 0.1459);

MVP

0.61

MPC

0.53

ClinPred

0.25

GERP RS

-8.4

Varity_R

0.11

gMVP

0.54

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over