Variant chr3-179811861-A-C 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_016559.3(PEX5L):c.1094T>G(p.Phe365Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000731 in 1,613,412 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00077 ( 1 hom. )

Consequence

PEX5L
NM_016559.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.98

Variant links:

Genes affected

PEX5L (HGNC:30024): (peroxisomal biogenesis factor 5 like) Enables peroxisome matrix targeting signal-1 binding activity and small GTPase binding activity. Predicted to be involved in protein import into peroxisome matrix, docking and regulation of cAMP-mediated signaling. Predicted to act upstream of or within maintenance of protein location and regulation of membrane potential. Located in cytosol. Part of receptor complex. [provided by Alliance of Genome Resources, Apr 2022]

PEX5L links:

PEX5L (HGNC:):

PEX5L 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=0.14743549).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PEX5L	NM_016559.3 linkuse as main transcript	c.1094T>G	p.Phe365Cys	missense_variant	11/15	ENST00000467460.6	NP_057643.1	Q8IYB4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PEX5L	ENST00000467460.6 linkuse as main transcript	c.1094T>G	p.Phe365Cys	missense_variant	11/15	1	NM_016559.3	ENSP00000419975.1		Q8IYB4-1

Frequencies

GnomAD3 genomes

AF:

0.000348

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000577

AC:

145

AN:

251470

Hom.:

AF XY:

0.000618

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000958

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000771

AC:

1127

AN:

1461078

Hom.:

Cov.:

AF XY:

0.000786

AC XY:

571

AN XY:

726910

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000962

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.000894

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.000348

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000617

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000586

Hom.:

Bravo

AF:

0.000431

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000758

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000763

EpiControl

AF:

0.00107

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.1094T>G (p.F365C) alteration is located in exon 11 (coding exon 11) of the PEX5L gene. This alteration results from a T to G substitution at nucleotide position 1094, causing the phenylalanine (F) at amino acid position 365 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.67

.;D;.;.;.;.;.;.;.

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.95

D;D;D;D;D;D;D;.;D

M_CAP

Benign

0.054

MetaRNN

Benign

0.15

T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.0

.;N;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-3.6

D;D;D;D;D;D;D;D;D

REVEL

Uncertain

0.29

Sift

Uncertain

0.025

D;D;D;D;D;D;D;D;T

Sift4G

Uncertain

0.020

D;D;D;D;D;D;D;D;D

Polyphen

0.99, 0.99, 0.97

.;D;D;D;.;.;.;.;.

Vest4

0.69

MVP

0.70

MPC

1.5

ClinPred

0.14

GERP RS

4.2

Varity_R

0.20

gMVP

0.72

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over