chrX-19645990-T-C

Variant names:

• chrX-19645990-T-C
• rs16981251
• NM_031892.3:c.727-515A>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.727-515A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 110,144 control chromosomes in the GnomAD database, including 3,032 homozygotes. There are 7,819 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 0.25 (3032 hom., 7819 hem., cov: 22)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.25
• 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: MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3KBP1	NM_031892.3	MANE Select	c.727-515A>G		intron	N/A	NP_114098.1	Q5JPT6
	SH3KBP1	NM_001410756.1		c.859-515A>G		intron	N/A	NP_001397685.1	Q5JPT2
	SH3KBP1	NM_001353891.2		c.802-515A>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.727-515A>G		intron	N/A	ENSP00000380921.3	Q96B97-1
	SH3KBP1	ENST00000379698.8	TSL:1	c.616-515A>G		intron	N/A	ENSP00000369020.4	Q96B97-2
	SH3KBP1	ENST00000379726.8	TSL:5	c.859-515A>G		intron	N/A	ENSP00000369049.4	Q5JPT2

Frequencies

GnomAD3 genomes AF: 0.251 AC: 27648 AN: 110087 Hom.: 3026 Cov.: 22

Gnomad AFR AF: 0.410

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.241

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

GnomAD4 genome AF: 0.251 AC: 27691 AN: 110144 Hom.: 3032 Cov.: 22 AF XY: 0.241 AC XY: 7819 AN XY: 32470

African (AFR) AF: 0.410 AC: 12362 AN: 30132

American (AMR) AF: 0.176 AC: 1843 AN: 10456

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 494 AN: 2628

East Asian (EAS) AF: 0.0169 AC: 59 AN: 3486

South Asian (SAS) AF: 0.160 AC: 410 AN: 2564

European-Finnish (FIN) AF: 0.278 AC: 1608 AN: 5788

Middle Eastern (MID) AF: 0.222 AC: 48 AN: 216

European-Non Finnish (NFE) AF: 0.195 AC: 10269 AN: 52703

Other (OTH) AF: 0.247 AC: 372 AN: 1506

Alfa AF: 0.209 Hom.: 4246

Bravo AF: 0.253

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.039
DANN	Benign	0.30
PhyloP100		-4.2
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: rs16981251; hg19: chrX-19664108;