Genetic Variant SH3KBP1:c.1893-8C>T (chrX-19537788-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_031892.3(SH3KBP1):c.1893-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,198,548 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000025 ( 0 hom. 5 hem. )

Consequence

SH3KBP1
NM_031892.3 splice_region, intron

Scores

Splicing: ADA: 0.00003640

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.37

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant X-19537788-G-A is Benign according to our data. Variant chrX-19537788-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3606352.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3KBP1	NM_031892.3 link	c.1893-8C>T		splice_region_variant, intron_variant	Intron 16 of 17	ENST00000397821.8	NP_114098.1	Q96B97-1Q5JPT6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3KBP1	ENST00000397821.8 link	c.1893-8C>T		splice_region_variant, intron_variant	Intron 16 of 17	1	NM_031892.3	ENSP00000380921.3		Q96B97-1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112053

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

34217

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000221

AC:

AN:

180807

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

65373

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000372

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000370

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000249

AC:

AN:

1086495

Hom.:

Cov.:

AF XY:

0.0000142

AC XY:

AN XY:

352109

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000287

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000312

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000178

AC:

AN:

112053

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

34217

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.9

DANN

Benign

0.55

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000036

dbscSNV1_RF

Benign

0.032

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over