rs4630061

Variant names:

• chrX-19659653-A-G
• rs4630061
• NM_031892.3:c.727-14178T>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.727-14178T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 111,864 control chromosomes in the GnomAD database, including 1,066 homozygotes. There are 5,049 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 0.15 (1066 hom., 5049 hem., cov: 23)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 0 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3KBP1	NM_031892.3	c.727-14178T>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.727-14178T>C		intron_variant	Intron 6 of 17	1	NM_031892.3	ENSP00000380921.3

Frequencies

GnomAD3 genomes AF: 0.155 AC: 17279 AN: 111809 Hom.: 1066 Cov.: 23

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0407

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.0675

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.155 AC: 17289 AN: 111864 Hom.: 1066 Cov.: 23 AF XY: 0.148 AC XY: 5049 AN XY: 34070

African (AFR) AF: 0.193 AC: 5943 AN: 30823

American (AMR) AF: 0.121 AC: 1281 AN: 10619

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 253 AN: 2659

East Asian (EAS) AF: 0.0173 AC: 62 AN: 3583

South Asian (SAS) AF: 0.0419 AC: 113 AN: 2694

European-Finnish (FIN) AF: 0.241 AC: 1444 AN: 5982

Middle Eastern (MID) AF: 0.0741 AC: 16 AN: 216

European-Non Finnish (NFE) AF: 0.148 AC: 7865 AN: 53089

Other (OTH) AF: 0.147 AC: 223 AN: 1520

Alfa AF: 0.146 Hom.: 6947

Bravo AF: 0.149

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.11
DANN	Benign	0.61
PhyloP100		-1.2
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: rs4630061; hg19: chrX-19677771;