Variant X-19537724-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_031892.3(SH3KBP1):c.1949G>A(p.Arg650Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00623 in 1,208,947 control chromosomes in the GnomAD database, including 26 homozygotes. There are 2,542 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R650W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0044 ( 0 hom., 145 hem., cov: 23)

Exomes 𝑓: 0.0064 ( 26 hom. 2397 hem. )

Consequence

SH3KBP1
NM_031892.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.35

Variant links:

Genes affected

SH3KBP1 (HGNC:13867): (SH3 domain containing kinase binding protein 1) This gene encodes an adapter protein that contains one or more N-terminal Src homology domains, a proline rich region and a C-terminal coiled-coil domain. The encoded protein facilitates protein-protein interactions and has been implicated in numerous cellular processes including apoptosis, cytoskeletal rearrangement, cell adhesion and in the regulation of clathrin-dependent endocytosis. Alternate splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2017]

SH3KBP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0070169866).

BP6

Variant X-19537724-C-T is Benign according to our data. Variant chrX-19537724-C-T is described in ClinVar as [Benign]. Clinvar id is 1166220.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-19537724-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd at 145 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3KBP1	NM_031892.3 linkuse as main transcript	c.1949G>A	p.Arg650Gln	missense_variant	17/18	ENST00000397821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3KBP1	ENST00000397821.8 linkuse as main transcript	c.1949G>A	p.Arg650Gln	missense_variant	17/18	1	NM_031892.3	P2	Q96B97-1

Frequencies

GnomAD3 genomes

AF:

0.00442

AC:

493

AN:

111461

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

145

AN XY:

33651

show subpopulations

Gnomad AFR

AF:

0.000947

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00114

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00823

Gnomad MID

AF:

0.0169

Gnomad NFE

AF:

0.00703

Gnomad OTH

AF:

0.00603

GnomAD3 exomes

AF:

0.00443

AC:

812

AN:

183337

Hom.:

AF XY:

0.00506

AC XY:

343

AN XY:

67777

show subpopulations

Gnomad AFR exome

AF:

0.000836

Gnomad AMR exome

AF:

0.00193

Gnomad ASJ exome

AF:

0.000801

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00441

Gnomad FIN exome

AF:

0.00681

Gnomad NFE exome

AF:

0.00637

Gnomad OTH exome

AF:

0.00618

GnomAD4 exome

AF:

0.00642

AC:

7043

AN:

1097435

Hom.:

Cov.:

AF XY:

0.00661

AC XY:

2397

AN XY:

362829

show subpopulations

Gnomad4 AFR exome

AF:

0.000947

Gnomad4 AMR exome

AF:

0.00216

Gnomad4 ASJ exome

AF:

0.000929

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.00584

Gnomad4 FIN exome

AF:

0.00664

Gnomad4 NFE exome

AF:

0.00714

Gnomad4 OTH exome

AF:

0.00610

GnomAD4 genome

AF:

0.00441

AC:

492

AN:

111512

Hom.:

Cov.:

AF XY:

0.00430

AC XY:

145

AN XY:

33712

show subpopulations

Gnomad4 AFR

AF:

0.000945

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00114

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.00823

Gnomad4 NFE

AF:

0.00703

Gnomad4 OTH

AF:

0.00595

Alfa

AF:

0.00636

Hom.:

279

Bravo

AF:

0.00373

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00865

AC:

ESP6500AA

AF:

0.00104

AC:

ESP6500EA

AF:

0.00624

AC:

ExAC

AF:

0.00466

AC:

566

EpiCase

AF:

0.00638

EpiControl

AF:

0.00741

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.16

T;.;.;T

FATHMM_MKL

Uncertain

0.86

LIST_S2

Pathogenic

0.98

D;D;D;D

MetaRNN

Benign

0.0070

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;.;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-0.74

N;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.063

T;T;T;T

Sift4G

Benign

0.46

T;T;T;T

Polyphen

1.0

D;.;.;.

Vest4

0.37

MVP

0.74

MPC

1.1

ClinPred

0.013

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.12

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