Variant 6-79696552-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_031469.4(SH3BGRL2):c.299G>A(p.Arg100Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000473 in 1,564,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

SH3BGRL2
NM_031469.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.65

Variant links:

Genes affected

SH3BGRL2 (HGNC:15567): (SH3 domain binding glutamate rich protein like 2) Predicted to enable SH3 domain binding activity. Located in nuclear membrane and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SH3BGRL2 links:

SH3BGRL2 (HGNC:):

SH3BGRL2 links:

Genome browser will be placed here

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=0.066474766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3BGRL2	NM_031469.4 linkuse as main transcript	c.299G>A	p.Arg100Gln	missense_variant	3/4	ENST00000369838.6	NP_113657.1	Q9UJC5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3BGRL2	ENST00000369838.6 linkuse as main transcript	c.299G>A	p.Arg100Gln	missense_variant	3/4	1	NM_031469.4	ENSP00000358853.4		Q9UJC5

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.000118

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000393

AC:

AN:

203372

Hom.:

AF XY:

0.0000359

AC XY:

AN XY:

111274

show subpopulations

Gnomad AFR exome

AF:

0.0000722

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:

0.0000703

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000460

AC:

AN:

1412224

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

702136

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:

0.0000131

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000556

Gnomad4 OTH exome

AF:

0.0000515

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151988

Hom.:

Cov.:

AF XY:

0.0000943

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.0000242

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:

0.000118

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000165

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000330

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

Nov 28, 2024

The c.299G>A (p.R100Q) alteration is located in exon 3 (coding exon 3) of the SH3BGRL2 gene. This alteration results from a G to A substitution at nucleotide position 299, causing the arginine (R) at amino acid position 100 to be replaced by a glutamine (Q). 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

0.062

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0059

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.82

M_CAP

Benign

0.0031

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.72

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.44

REVEL

Benign

0.13

Sift

Benign

0.17

Sift4G

Benign

0.24

Polyphen

0.0010

Vest4

0.19

MutPred

0.32

Gain of ubiquitination at K98 (P = 0.0261);

MVP

0.095

MPC

0.22

ClinPred

0.051

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.052

gMVP

0.28

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