Variant 19-7477242-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080662.4(PEX11G):c.686C>T(p.Ala229Val) variant causes a missense change. The variant allele was found at a frequency of 0.00035 in 1,558,832 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00036 ( 1 hom. )

Consequence

PEX11G
NM_080662.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.93

Variant links:

Genes affected

PEX11G (HGNC:20208): (peroxisomal biogenesis factor 11 gamma) The protein encoded by this gene is a member of the PEX11 family. This family is reported to regulate the number and size of peroxisomes in evolutionarily distant organisms. The protein encoded by this gene may induce clustering of peroxisomes. Alternative splicing results in multiple transcript variants that encode different protein isoforms. [provided by RefSeq, Jul 2012]

PEX11G links:

ARHGEF18 (HGNC:):

ARHGEF18 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011449516).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX11G	NM_080662.4 linkuse as main transcript	c.686C>T	p.Ala229Val	missense_variant	5/5	ENST00000221480.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PEX11G	ENST00000221480.6 linkuse as main transcript	c.686C>T	p.Ala229Val	missense_variant	5/5	1	NM_080662.4	P1	Q96HA9-1
PEX11G	ENST00000593942.5 linkuse as main transcript	c.476C>T	p.Ala159Val	missense_variant	7/7	5			Q96HA9-2
PEX11G	ENST00000593547.1 linkuse as main transcript	c.467C>T	p.Ala156Val	missense_variant	5/5	5
PEX11G	ENST00000599519.1 linkuse as main transcript	n.488C>T		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000566

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000277

AC:

AN:

176882

Hom.:

AF XY:

0.000297

AC XY:

AN XY:

97518

show subpopulations

Gnomad AFR exome

AF:

0.0000945

Gnomad AMR exome

AF:

0.000213

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000310

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000805

Gnomad NFE exome

AF:

0.000316

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.000358

AC:

504

AN:

1406552

Hom.:

Cov.:

AF XY:

0.000373

AC XY:

260

AN XY:

696670

show subpopulations

Gnomad4 AFR exome

AF:

0.0000319

Gnomad4 AMR exome

AF:

0.000205

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000108

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.000568

Gnomad4 NFE exome

AF:

0.000417

Gnomad4 OTH exome

AF:

0.000156

GnomAD4 genome

AF:

0.000276

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000566

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000129

Hom.:

Bravo

AF:

0.000261

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000472

AC:

ExAC

AF:

0.000235

AC:

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

May 08, 2023

The c.686C>T (p.A229V) alteration is located in exon 5 (coding exon 5) of the PEX11G gene. This alteration results from a C to T substitution at nucleotide position 686, causing the alanine (A) at amino acid position 229 to be replaced by a valine (V). 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

0.098

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0093

T;.

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.087

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.011

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.95

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.88

N;.

REVEL

Benign

0.076

Sift

Benign

0.29

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.031

B;.

Vest4

0.15

MVP

0.21

MPC

0.056

ClinPred

0.035

GERP RS

4.0

Varity_R

0.062

gMVP

0.41

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