Variant chr9-129012237-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_020145.4(SH3GLB2):c.623C>T(p.Ala208Val) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000194 in 1,290,894 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 2 hom. )

Consequence

SH3GLB2
NM_020145.4 missense, splice_region

Scores

Splicing: ADA: 0.9919

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.99

Variant links:

Genes affected

SH3GLB2 (HGNC:10834): (SH3 domain containing GRB2 like, endophilin B2) Enables identical protein binding activity. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SH3GLB2 links:

SH3GLB2 (HGNC:):

SH3GLB2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3GLB2	NM_020145.4 linkuse as main transcript	c.623C>T	p.Ala208Val	missense_variant, splice_region_variant	6/11	ENST00000372564.8	NP_064530.1	Q9NR46-1A0A024R896

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3GLB2	ENST00000372564.8 linkuse as main transcript	c.623C>T	p.Ala208Val	missense_variant, splice_region_variant	6/11	1	NM_020145.4	ENSP00000361645.3		Q9NR46-1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000220

AC:

AN:

58974

Hom.:

AF XY:

0.000307

AC XY:

AN XY:

29290

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:

0.000363

Gnomad OTH exome

AF:

0.00105

GnomAD4 exome

AF:

0.000192

AC:

219

AN:

1138788

Hom.:

Cov.:

AF XY:

0.000186

AC XY:

101

AN XY:

542394

show subpopulations

Gnomad4 AFR exome

AF:

0.000611

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000336

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000148

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000154

Gnomad4 OTH exome

AF:

0.000371

GnomAD4 genome

AF:

0.000210

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000491

Hom.:

Bravo

AF:

0.000317

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.000350

AC:

ExAC

AF:

0.000175

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

Sep 17, 2021

The c.623C>T (p.A208V) alteration is located in exon 6 (coding exon 6) of the SH3GLB2 gene. This alteration results from a C to T substitution at nucleotide position 623, causing the alanine (A) at amino acid position 208 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

0.26

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.052

T;T;.;T

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

0.98

.;D;D;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.31

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;M;.;.

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.46

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.25

T;T;T;T

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.91

P;P;D;.

Vest4

0.65

MVP

0.61

MPC

0.85

ClinPred

0.18

GERP RS

5.8

Varity_R

0.14

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.88

SpliceAI score (max)

0.020

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