rs781779718

Variant names:

• chrX-19541910-T-A
• rs781779718
• NM_031892.3:c.1892+15A>T

Your query was ambiguous. Multiple possible variants found:

• chrX-19541910-T-A
• chrX-19541910-T-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_031892.3(SH3KBP1):​c.1892+15A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,191,231 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.000010 (0 hom. 3 hem.)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.872
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant X-19541910-T-A is Benign according to our data. Variant chrX-19541910-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1628402.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAdExome4 at 3 XL,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031892.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3KBP1	NM_031892.3	MANE Select	c.1892+15A>T		intron	N/A	NP_114098.1	Q5JPT6
	SH3KBP1	NM_001410756.1		c.2024+15A>T		intron	N/A	NP_001397685.1	Q5JPT2
	SH3KBP1	NM_001353891.2		c.1967+15A>T		intron	N/A	NP_001340820.1	A0A8V8TP27

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3KBP1	ENST00000397821.8	TSL:1 MANE Select	c.1892+15A>T		intron	N/A	ENSP00000380921.3	Q96B97-1
	SH3KBP1	ENST00000379698.8	TSL:1	c.1781+15A>T		intron	N/A	ENSP00000369020.4	Q96B97-2
	SH3KBP1	ENST00000379726.8	TSL:5	c.2024+15A>T		intron	N/A	ENSP00000369049.4	Q5JPT2

Frequencies

GnomAD3 genomes AF: 0.0000182 AC: 2 AN: 110086 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000191

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000544 AC: 9 AN: 165330 AF XY: 0.0000565

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000352

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000102 AC: 11 AN: 1081145 Hom.: 0 Cov.: 31 AF XY: 0.00000856 AC XY: 3 AN XY: 350567

African (AFR) AF: 0.00 AC: 0 AN: 25991

American (AMR) AF: 0.000265 AC: 9 AN: 34023

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18424

East Asian (EAS) AF: 0.00 AC: 0 AN: 29701

South Asian (SAS) AF: 0.00 AC: 0 AN: 51526

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39977

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4044

European-Non Finnish (NFE) AF: 0.00000120 AC: 1 AN: 832131

Other (OTH) AF: 0.0000221 AC: 1 AN: 45328

GnomAD4 genome AF: 0.0000182 AC: 2 AN: 110086 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 32582

African (AFR) AF: 0.00 AC: 0 AN: 30217

American (AMR) AF: 0.000191 AC: 2 AN: 10449

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2624

East Asian (EAS) AF: 0.00 AC: 0 AN: 3476

South Asian (SAS) AF: 0.00 AC: 0 AN: 2496

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 239

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52585

Other (OTH) AF: 0.00 AC: 0 AN: 1477

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000453

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.86
DANN	Benign	0.40
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism

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: rs781779718; hg19: chrX-19560028;