rs373915090

Variant names:

• chrX-19536474-T-C
• rs373915090
• NM_031892.3:c.1957-16A>G

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.1957-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000332 in 1,083,762 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 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 0.00012 (0 hom., 5 hem., cov: 23)
  • Exomes 𝑓: 0.000024 (0 hom. 3 hem.)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.294
• 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=-0.83).
• BP6: Variant X-19536474-T-C is Benign according to our data. Variant chrX-19536474-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1547827.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 5 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.1957-16A>G		intron	N/A	NP_114098.1	Q5JPT6
	SH3KBP1	NM_001410756.1		c.2089-16A>G		intron	N/A	NP_001397685.1	Q5JPT2
	SH3KBP1	NM_001353891.2		c.2032-16A>G		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.1957-16A>G		intron	N/A	ENSP00000380921.3	Q96B97-1
	SH3KBP1	ENST00000379698.8	TSL:1	c.1846-16A>G		intron	N/A	ENSP00000369020.4	Q96B97-2
	SH3KBP1	ENST00000379726.8	TSL:5	c.2089-16A>G		intron	N/A	ENSP00000369049.4	Q5JPT2

Frequencies

GnomAD3 genomes AF: 0.000117 AC: 13 AN: 111453 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000424

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000693 AC: 11 AN: 158679 AF XY: 0.0000607

Gnomad AFR exome AF: 0.000839

Gnomad AMR exome AF: 0.0000461

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: 0.0000237 AC: 23 AN: 972255 Hom.: 0 Cov.: 17 AF XY: 0.0000110 AC XY: 3 AN XY: 272905

African (AFR) AF: 0.000804 AC: 19 AN: 23643

American (AMR) AF: 0.0000968 AC: 3 AN: 30990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17819

East Asian (EAS) AF: 0.00 AC: 0 AN: 28582

South Asian (SAS) AF: 0.00 AC: 0 AN: 45888

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 740224

Other (OTH) AF: 0.0000241 AC: 1 AN: 41497

GnomAD4 genome AF: 0.000117 AC: 13 AN: 111507 Hom.: 0 Cov.: 23 AF XY: 0.000148 AC XY: 5 AN XY: 33765

African (AFR) AF: 0.000423 AC: 13 AN: 30713

American (AMR) AF: 0.00 AC: 0 AN: 10500

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.00 AC: 0 AN: 3557

South Asian (SAS) AF: 0.00 AC: 0 AN: 2674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5915

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53088

Other (OTH) AF: 0.00 AC: 0 AN: 1515

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000215

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	-0.83
CADD	Benign	11
DANN	Benign	0.62
PhyloP100		0.29
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: rs373915090; hg19: chrX-19554592;