Variant chr19-7477206-G-T 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_080662.4(PEX11G):c.722C>A(p.Pro241His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000968 in 1,342,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000097 ( 0 hom. )

Consequence

PEX11G
NM_080662.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0280

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:

Genome browser will be placed here

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=0.19220987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PEX11G	NM_080662.4 linkuse as main transcript	c.722C>A	p.Pro241His	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.722C>A	p.Pro241His	missense_variant	5/5	1	NM_080662.4	P1	Q96HA9-1
PEX11G	ENST00000593942.5 linkuse as main transcript	c.512C>A	p.Pro171His	missense_variant	7/7	5			Q96HA9-2
PEX11G	ENST00000593547.1 linkuse as main transcript	c.503C>A	p.Pro168His	missense_variant	5/5	5
PEX11G	ENST00000599519.1 linkuse as main transcript	n.524C>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000968

AC:

AN:

1342360

Hom.:

Cov.:

AF XY:

0.00000912

AC XY:

AN XY:

658160

show subpopulations

Gnomad4 AFR exome

AF:

0.000204

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000146

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000725

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 26, 2022

The c.722C>A (p.P241H) alteration is located in exon 5 (coding exon 5) of the PEX11G gene. This alteration results from a C to A substitution at nucleotide position 722, causing the proline (P) at amino acid position 241 to be replaced by a histidine (H). 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

0.11

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0050

T;.

Eigen

Benign

-0.021

Eigen_PC

Benign

-0.037

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.45

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

0.95

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.64

N;.

REVEL

Benign

0.10

Sift

Pathogenic

0.0

D;.

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.98

D;.

Vest4

0.18

MutPred

0.25

Loss of glycosylation at P241 (P = 0.0173);.;

MVP

0.33

MPC

0.21

ClinPred

0.61

GERP RS

5.0

Varity_R

0.15

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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