NM_031892.3:c.1384+4834G>C

Variant names:

• chrX-19564269-C-G
• rs7051590
• NM_031892.3:c.1384+4834G>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.1384+4834G>C 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 110,975 control chromosomes in the GnomAD database, including 4,847 homozygotes. There are 8,851 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 (4847 hom., 8851 hem., cov: 22)
• Consequence: SH3KBP1 NM_031892.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0360
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 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.1384+4834G>C		intron	N/A	NP_114098.1
	SH3KBP1	NM_001410756.1		c.1516+4834G>C		intron	N/A	NP_001397685.1
	SH3KBP1	NM_001353891.2		c.1459+4834G>C		intron	N/A	NP_001340820.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3KBP1	ENST00000397821.8	TSL:1 MANE Select	c.1384+4834G>C		intron	N/A	ENSP00000380921.3
	SH3KBP1	ENST00000379698.8	TSL:1	c.1273+4834G>C		intron	N/A	ENSP00000369020.4
	SH3KBP1	ENST00000379726.8	TSL:5	c.1516+4834G>C		intron	N/A	ENSP00000369049.4

Frequencies

GnomAD3 genomes AF: 0.279 AC: 30985 AN: 110920 Hom.: 4842 Cov.: 22

Gnomad AFR AF: 0.600

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.177

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0266

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.157

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.280 AC: 31048 AN: 110975 Hom.: 4847 Cov.: 22 AF XY: 0.266 AC XY: 8851 AN XY: 33255

African (AFR) AF: 0.600 AC: 18197 AN: 30317

American (AMR) AF: 0.177 AC: 1859 AN: 10522

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 323 AN: 2638

East Asian (EAS) AF: 0.0266 AC: 95 AN: 3566

South Asian (SAS) AF: 0.0788 AC: 210 AN: 2664

European-Finnish (FIN) AF: 0.252 AC: 1488 AN: 5903

Middle Eastern (MID) AF: 0.148 AC: 32 AN: 216

European-Non Finnish (NFE) AF: 0.157 AC: 8288 AN: 52944

Other (OTH) AF: 0.270 AC: 412 AN: 1527

Alfa AF: 0.109 Hom.: 546

Bravo AF: 0.291

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.6
DANN	Benign	0.48
PhyloP100		-0.036
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: rs7051590; hg19: chrX-19582387;