Variant 6-79696551-C-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_031469.4(SH3BGRL2):c.298C>T(p.Arg100Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000851 in 1,563,602 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 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000086 ( 1 hom. )

Consequence

SH3BGRL2
NM_031469.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.692

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:

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=0.09259206).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BGRL2	NM_031469.4 linkuse as main transcript	c.298C>T	p.Arg100Trp	missense_variant	3/4	ENST00000369838.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BGRL2	ENST00000369838.6 linkuse as main transcript	c.298C>T	p.Arg100Trp	missense_variant	3/4	1	NM_031469.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000153

AC:

AN:

203234

Hom.:

AF XY:

0.0000989

AC XY:

AN XY:

111228

show subpopulations

Gnomad AFR exome

AF:

0.000144

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000430

Gnomad SAS exome

AF:

0.0000456

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000804

Gnomad OTH exome

AF:

0.000641

GnomAD4 exome

AF:

0.0000857

AC:

121

AN:

1411554

Hom.:

Cov.:

AF XY:

0.0000983

AC XY:

AN XY:

701868

show subpopulations

Gnomad4 AFR exome

AF:

0.000168

Gnomad4 AMR exome

AF:

0.000624

Gnomad4 ASJ exome

AF:

0.0000406

Gnomad4 EAS exome

AF:

0.000323

Gnomad4 SAS exome

AF:

0.0000392

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000602

Gnomad4 OTH exome

AF:

0.000172

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152048

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000954

Hom.:

Bravo

AF:

0.000140

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000214

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 16, 2021

The c.298C>T (p.R100W) alteration is located in exon 3 (coding exon 3) of the SH3BGRL2 gene. This alteration results from a C to T substitution at nucleotide position 298, causing the arginine (R) at amino acid position 100 to be replaced by a tryptophan (W). 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

0.092

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.24

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.090

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.56

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.011

MetaRNN

Benign

0.093

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.87

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.37

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0060

Polyphen

0.97

Vest4

0.38

MVP

0.17

MPC

0.37

ClinPred

0.056

GERP RS

-0.33

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.14

gMVP

0.41

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