X-19541911-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_031892.3(SH3KBP1):c.1892+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00622 in 1,196,833 control chromosomes in the GnomAD database, including 173 homozygotes. There are 2,358 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (87 hom., 763 hem., cov: 22)
  • Exomes 𝑓: 0.0043 (86 hom. 1595 hem.)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.29

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant X-19541911-C-T is Benign according to our data. Variant chrX-19541911-C-T is described in ClinVar as [Benign]. Clinvar id is 1167394.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0824 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3KBP1	NM_031892.3	c.1892+14G>A		intron_variant		ENST00000397821.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3KBP1	ENST00000397821.8	c.1892+14G>A		intron_variant		1	NM_031892.3	P2

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 2821 AN: 111654 Hom.: 88 Cov.: 22 AF XY: 0.0226 AC XY: 763 AN XY: 33832

Gnomad AFR AF: 0.0852

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.00226

Gnomad EAS AF: 0.00450

Gnomad SAS AF: 0.0155

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00420

Gnomad NFE AF: 0.000527

Gnomad OTH AF: 0.0192

GnomAD3 exomes AF: 0.00999 AC: 1672 AN: 167393 Hom.: 38 AF XY: 0.00828 AC XY: 453 AN XY: 54689

Gnomad AFR exome AF: 0.0854

Gnomad AMR exome AF: 0.00610

Gnomad ASJ exome AF: 0.00403

Gnomad EAS exome AF: 0.00218

Gnomad SAS exome AF: 0.0203

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000296

Gnomad OTH exome AF: 0.00511

GnomAD4 exome AF: 0.00426 AC: 4620 AN: 1085127 Hom.: 86 Cov.: 31 AF XY: 0.00451 AC XY: 1595 AN XY: 353567

Gnomad4 AFR exome AF: 0.0866

Gnomad4 AMR exome AF: 0.00640

Gnomad4 ASJ exome AF: 0.00393

Gnomad4 EAS exome AF: 0.0168

Gnomad4 SAS exome AF: 0.0208

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000132

Gnomad4 OTH exome AF: 0.00760

GnomAD4 genome AF: 0.0253 AC: 2822 AN: 111706 Hom.: 87 Cov.: 22 AF XY: 0.0225 AC XY: 763 AN XY: 33894

Gnomad4 AFR AF: 0.0851

Gnomad4 AMR AF: 0.00856

Gnomad4 ASJ AF: 0.00226

Gnomad4 EAS AF: 0.00452

Gnomad4 SAS AF: 0.0151

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000528

Gnomad4 OTH AF: 0.0190

Alfa AF: 0.00634 Hom.: 167

Bravo AF: 0.0288

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.3
Dann	Benign	0.28

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: rs7064946; hg19: chrX-19560029;