X-19581746-T-C

Variant names:

• chrX-19581746-T-C
• rs5955820
• NM_031892.3:c.1298+6897A>G

Variant summary

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

The NM_031892.3(SH3KBP1):​c.1298+6897A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 108,124 control chromosomes in the GnomAD database, including 3,872 homozygotes. There are 8,175 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 0.28 (3872 hom., 8175 hem., cov: 21)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255
• Publications: 1 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=-0.55).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3KBP1	NM_031892.3	MANE Select	c.1298+6897A>G		intron	N/A	NP_114098.1
	SH3KBP1	NM_001410756.1		c.1430+6897A>G		intron	N/A	NP_001397685.1
	SH3KBP1	NM_001353891.2		c.1373+6897A>G		intron	N/A	NP_001340820.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3KBP1	ENST00000397821.8	TSL:1 MANE Select	c.1298+6897A>G		intron	N/A	ENSP00000380921.3
	SH3KBP1	ENST00000379698.8	TSL:1	c.1187+6897A>G		intron	N/A	ENSP00000369020.4
	SH3KBP1	ENST00000379726.8	TSL:5	c.1430+6897A>G		intron	N/A	ENSP00000369049.4

Frequencies

GnomAD3 genomes AF: 0.280 AC: 30241 AN: 108080 Hom.: 3868 Cov.: 21

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.0242

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.280 AC: 30267 AN: 108124 Hom.: 3872 Cov.: 21 AF XY: 0.267 AC XY: 8175 AN XY: 30600

African (AFR) AF: 0.490 AC: 14427 AN: 29461

American (AMR) AF: 0.196 AC: 1964 AN: 10029

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 503 AN: 2612

East Asian (EAS) AF: 0.0240 AC: 83 AN: 3454

South Asian (SAS) AF: 0.218 AC: 540 AN: 2479

European-Finnish (FIN) AF: 0.273 AC: 1482 AN: 5430

Middle Eastern (MID) AF: 0.266 AC: 55 AN: 207

European-Non Finnish (NFE) AF: 0.204 AC: 10680 AN: 52310

Other (OTH) AF: 0.271 AC: 398 AN: 1471

Alfa AF: 0.180 Hom.: 1843

Bravo AF: 0.286

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	9.3
DANN	Benign	0.91
PhyloP100		-0.26
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: rs5955820; hg19: chrX-19599864;