X-19581746-T-C

Position:

• chrX-19581746-T-C

Variant summary

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

The ENST00000397821.8(SH3KBP1):​c.1298+6897A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 108,124 control chromosomes in the GnomAD database, including 3,872 homozygotes. There are 8,175 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 0.28 (3872 hom., 8175 hem., cov: 21)
• Consequence: SH3KBP1 ENST00000397821.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3KBP1	NM_031892.3	c.1298+6897A>G		intron_variant		ENST00000397821.8	NP_114098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3KBP1	ENST00000397821.8	c.1298+6897A>G		intron_variant		1	NM_031892.3	ENSP00000380921	P2

Frequencies

GnomAD3 genomes AF: 0.280 AC: 30241 AN: 108080 Hom.: 3868 Cov.: 21 AF XY: 0.267 AC XY: 8162 AN XY: 30548

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0242

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.280 AC: 30267 AN: 108124 Hom.: 3872 Cov.: 21 AF XY: 0.267 AC XY: 8175 AN XY: 30600

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.0240

Gnomad4 SAS AF: 0.218

Gnomad4 FIN AF: 0.273

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.271

Alfa AF: 0.180 Hom.: 1843

Bravo AF: 0.286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.3
DANN	Benign	0.91

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: rs5955820; hg19: chrX-19599864;