rs12013533

Variant names:

• chrX-19543735-T-C
• rs12013533
• NM_031892.3:c.1624-1542A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-19543735-T-C
• chrX-19543735-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_031892.3(SH3KBP1):​c.1624-1542A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 109,529 control chromosomes in the GnomAD database, including 3,132 homozygotes. There are 8,191 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 0.26 (3132 hom., 8191 hem., cov: 22)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.19
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3KBP1	NM_031892.3	c.1624-1542A>G		intron_variant	Intron 15 of 17	ENST00000397821.8	NP_114098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3KBP1	ENST00000397821.8	c.1624-1542A>G		intron_variant	Intron 15 of 17	1	NM_031892.3	ENSP00000380921.3

Frequencies

GnomAD3 genomes AF: 0.264 AC: 28953 AN: 109474 Hom.: 3127 Cov.: 22

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.0773

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.265 AC: 28979 AN: 109529 Hom.: 3132 Cov.: 22 AF XY: 0.256 AC XY: 8191 AN XY: 31945

African (AFR) AF: 0.387 AC: 11612 AN: 29996

American (AMR) AF: 0.193 AC: 1998 AN: 10378

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 539 AN: 2622

East Asian (EAS) AF: 0.0773 AC: 267 AN: 3456

South Asian (SAS) AF: 0.208 AC: 530 AN: 2552

European-Finnish (FIN) AF: 0.288 AC: 1660 AN: 5758

Middle Eastern (MID) AF: 0.269 AC: 58 AN: 216

European-Non Finnish (NFE) AF: 0.224 AC: 11760 AN: 52408

Other (OTH) AF: 0.270 AC: 400 AN: 1483

Alfa AF: 0.238 Hom.: 18014

Bravo AF: 0.265

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.13
DANN	Benign	0.41
PhyloP100		-3.2
Mutation Taster		=99/1	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: rs12013533; hg19: chrX-19561853;