Variant chr3-15258965-A-G 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_004844.5(SH3BP5):c.755T>C(p.Met252Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,834 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SH3BP5
NM_004844.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.49

Variant links:

Genes affected

SH3BP5 (HGNC:10827): (SH3 domain binding protein 5) Enables guanyl-nucleotide exchange factor activity and protein kinase inhibitor activity. Acts upstream of or within intracellular signal transduction. Located in cytoplasmic vesicle membrane and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

SH3BP5 links:

SH3BP5-AS1 (HGNC:44501): (SH3BP5 antisense RNA 1)

SH3BP5-AS1 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=0.06079942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3BP5	NM_004844.5 linkuse as main transcript	c.755T>C	p.Met252Thr	missense_variant	7/9	ENST00000383791.8
SH3BP5-AS1	NR_046084.1 linkuse as main transcript	n.3755A>G		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP5	ENST00000383791.8 linkuse as main transcript	c.755T>C	p.Met252Thr	missense_variant	7/9	1	NM_004844.5	P1	O60239-1
SH3BP5-AS1	ENST00000420195.1 linkuse as main transcript	n.3755A>G		non_coding_transcript_exon_variant	2/3	1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152202

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000636

AC:

AN:

251456

Hom.:

AF XY:

0.0000294

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000463

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461834

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.0000741

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.10

T;.;.;T

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.76

T;.;T;T

M_CAP

Benign

0.036

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;.;.;.

MutationTaster

Benign

0.55

N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.50

N;N;N;N

REVEL

Benign

0.037

Sift

Benign

0.60

T;T;T;T

Sift4G

Benign

0.59

T;T;T;T

Polyphen

0.0

B;.;.;.

Vest4

0.32

MutPred

0.38

Gain of glycosylation at S254 (P = 0.0291);.;.;.;

MVP

0.71

MPC

0.058

ClinPred

0.020

GERP RS

3.1

Varity_R

0.13

gMVP

0.12

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over