X-19660540-A-G

Variant names:

• chrX-19660540-A-G
• rs11795873
• NM_031892.3:c.727-15065T>C

Variant summary

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

The NM_031892.3(SH3KBP1):​c.727-15065T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 110,591 control chromosomes in the GnomAD database, including 5,960 homozygotes. There are 11,688 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 0.34 (5960 hom., 11688 hem., cov: 22)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3KBP1	NM_031892.3	c.727-15065T>C		intron_variant	Intron 6 of 17	ENST00000397821.8	NP_114098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3KBP1	ENST00000397821.8	c.727-15065T>C		intron_variant	Intron 6 of 17	1	NM_031892.3	ENSP00000380921.3

Frequencies

GnomAD3 genomes AF: 0.345 AC: 38091 AN: 110539 Hom.: 5964 Cov.: 22

Gnomad AFR AF: 0.0778

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.807

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.344 AC: 38079 AN: 110591 Hom.: 5960 Cov.: 22 AF XY: 0.356 AC XY: 11688 AN XY: 32839

African (AFR) AF: 0.0777 AC: 2383 AN: 30657

American (AMR) AF: 0.580 AC: 5995 AN: 10339

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1382 AN: 2638

East Asian (EAS) AF: 0.807 AC: 2796 AN: 3466

South Asian (SAS) AF: 0.744 AC: 1919 AN: 2579

European-Finnish (FIN) AF: 0.375 AC: 2159 AN: 5763

Middle Eastern (MID) AF: 0.355 AC: 77 AN: 217

European-Non Finnish (NFE) AF: 0.389 AC: 20501 AN: 52756

Other (OTH) AF: 0.372 AC: 562 AN: 1509

Alfa AF: 0.398 Hom.: 40329

Bravo AF: 0.355

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.6
DANN	Benign	0.80
PhyloP100		1.4
Mutation Taster		=100/0	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: rs11795873; hg19: chrX-19678658;