rs11094775

Variant names:

• chrX-19710987-C-T
• rs11094775
• NM_031892.3:c.287-4003G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• immunodeficiency 61

  Inheritance: XL, Unknown Classification: LIMITED Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031892.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3KBP1	NM_031892.3	MANE Select	c.287-4003G>A		intron	N/A	NP_114098.1
	SH3KBP1	NM_001410756.1		c.287-4003G>A		intron	N/A	NP_001397685.1
	SH3KBP1	NM_001353891.2		c.287-4003G>A		intron	N/A	NP_001340820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3KBP1	ENST00000397821.8	TSL:1 MANE Select	c.287-4003G>A		intron	N/A	ENSP00000380921.3
	SH3KBP1	ENST00000379698.8	TSL:1	c.176-4003G>A		intron	N/A	ENSP00000369020.4
	SH3KBP1	ENST00000379726.8	TSL:5	c.287-4003G>A		intron	N/A	ENSP00000369049.4

Frequencies

GnomAD3 genomes AF: 0.343 AC: 37928 AN: 110479 Hom.: 8750 Cov.: 22

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

African (AFR) AF: 0.843 AC: 25402 AN: 30131

American (AMR) AF: 0.201 AC: 2089 AN: 10404

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 319 AN: 2641

East Asian (EAS) AF: 0.0218 AC: 77 AN: 3540

South Asian (SAS) AF: 0.0497 AC: 132 AN: 2658

European-Finnish (FIN) AF: 0.248 AC: 1446 AN: 5831

Middle Eastern (MID) AF: 0.145 AC: 31 AN: 214

European-Non Finnish (NFE) AF: 0.150 AC: 7915 AN: 52924

Other (OTH) AF: 0.304 AC: 459 AN: 1510

Alfa AF: 0.215 Hom.: 12571

Bravo AF: 0.365

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.31
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11094775; hg19: chrX-19729105;