rs7051590

Positions:

• chrX-19564269-C-G
• chrX-19564269-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.1384+4834G>C 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 110,975 control chromosomes in the GnomAD database, including 4,847 homozygotes. There are 8,851 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 (4847 hom., 8851 hem., cov: 22)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3KBP1	NM_031892.3	c.1384+4834G>C		intron_variant		ENST00000397821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3KBP1	ENST00000397821.8	c.1384+4834G>C		intron_variant		1	NM_031892.3	P2

Frequencies

GnomAD3 genomes AF: 0.279 AC: 30985 AN: 110920 Hom.: 4842 Cov.: 22 AF XY: 0.265 AC XY: 8804 AN XY: 33190

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.280 AC: 31048 AN: 110975 Hom.: 4847 Cov.: 22 AF XY: 0.266 AC XY: 8851 AN XY: 33255

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.177

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0266

Gnomad4 SAS AF: 0.0788

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.157

Gnomad4 OTH AF: 0.270

Alfa AF: 0.109 Hom.: 546

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.48

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: rs7051590; hg19: chrX-19582387;