rs12013533

chrX-19543735-T-CchrX-19543735-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.91).
• 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/exons	MANE	UniProt
SH3KBP1	NM_031892.3	c.1624-1542A>G		intron_variant		ENST00000397821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3KBP1	ENST00000397821.8	c.1624-1542A>G		intron_variant		1	NM_031892.3	P2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 28953 AN: 109474 Hom.: 3127 Cov.: 22 AF XY: 0.256 AC XY: 8171 AN XY: 31884

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

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.206

Gnomad4 EAS AF: 0.0773

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.270

Alfa AF: 0.230 Hom.: 12299

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

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: rs12013533; hg19: chrX-19561853;