rs11094775

chrX-19710987-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031892.3(SH3KBP1):c.287-4003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 110,532 control chromosomes in the GnomAD database, including 8,758 homozygotes. There are 10,583 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (8758 hom., 10583 hem., cov: 22)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3KBP1	NM_031892.3	c.287-4003G>A		intron_variant		ENST00000397821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3KBP1	ENST00000397821.8	c.287-4003G>A		intron_variant		1	NM_031892.3	P2

Frequencies

GnomAD3 genomes AF: 0.343 AC: 37928 AN: 110479 Hom.: 8750 Cov.: 22 AF XY: 0.322 AC XY: 10534 AN XY: 32719

Gnomad AFR AF: 0.843

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.0484

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.344 AC: 37997 AN: 110532 Hom.: 8758 Cov.: 22 AF XY: 0.323 AC XY: 10583 AN XY: 32782

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.121

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.0497

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.150

Gnomad4 OTH AF: 0.304

Alfa AF: 0.184 Hom.: 7804

Bravo AF: 0.365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.14
Dann	Benign	0.31

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

Other links and lift over

dbSNP: rs11094775; hg19: chrX-19729105;