Variant chr1-26280162-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_031286.4(SH3BGRL3):c.7G>T(p.Gly3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SH3BGRL3
NM_031286.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.83

Variant links:

Genes affected

SH3BGRL3 (HGNC:15568): (SH3 domain binding glutamate rich protein like 3) Located in nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

SH3BGRL3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3103359).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BGRL3	NM_031286.4 linkuse as main transcript	c.7G>T	p.Gly3Cys	missense_variant	1/3	ENST00000270792.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BGRL3	ENST00000270792.10 linkuse as main transcript	c.7G>T	p.Gly3Cys	missense_variant	1/3	1	NM_031286.4	P1
SH3BGRL3	ENST00000319041.6 linkuse as main transcript	c.7G>T	p.Gly3Cys	missense_variant	1/2	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000599

AC:

AN:

166844

Hom.:

AF XY:

0.0000109

AC XY:

AN XY:

92150

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000835

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412870

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

699706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000273

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

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

Sep 07, 2022

The c.7G>T (p.G3C) alteration is located in exon 1 (coding exon 1) of the SH3BGRL3 gene. This alteration results from a G to T substitution at nucleotide position 7, causing the glycine (G) at amino acid position 3 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.67

T;T

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.31

T;T

MetaSVM

Benign

-0.39

MutationTaster

Benign

0.98

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-1.4

N;N

REVEL

Uncertain

0.34

Sift

Uncertain

0.016

D;D

Sift4G

Uncertain

0.020

D;D

Polyphen

0.85

P;.

Vest4

0.16

MutPred

0.50

Gain of catalytic residue at M1 (P = 2e-04);Gain of catalytic residue at M1 (P = 2e-04);

MVP

0.64

MPC

0.37

ClinPred

0.99

GERP RS

5.1

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.7

Varity_R

0.27

gMVP

0.63

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