Genetic Variant SH3BP5:p.Asp385fs (chr3-15256289-CTTCTGCCCTGTCTCCTATAGAAATACAAGGATTATCAAAAGTGAGTATTGACAA-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_004844.5(SH3BP5):c.1151-40_1164delTTGTCAATACTCACTTTTGATAATCCTTGTATTTCTATAGGAGACAGGGCAGAA(p.Asp385fs) variant causes a frameshift, splice acceptor, splice region, intron change. The variant allele was found at a frequency of 0.00239 in 152,270 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

SH3BP5
NM_004844.5 frameshift, splice_acceptor, splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.90

Variant links:

Genes affected

SH3BP5 (HGNC:10827): (SH3 domain binding protein 5) Enables guanyl-nucleotide exchange factor activity and protein kinase inhibitor activity. Acts upstream of or within intracellular signal transduction. Located in cytoplasmic vesicle membrane and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

SH3BP5 links:

SH3BP5-AS1 (HGNC:44501): (SH3BP5 antisense RNA 1)

SH3BP5-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 3-15256289-CTTCTGCCCTGTCTCCTATAGAAATACAAGGATTATCAAAAGTGAGTATTGACAA-C is Benign according to our data. Variant chr3-15256289-CTTCTGCCCTGTCTCCTATAGAAATACAAGGATTATCAAAAGTGAGTATTGACAA-C is described in ClinVar as [Likely_benign]. Clinvar id is 735908.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3BP5	NM_004844.5 link	c.1151-40_1164delTTGTCAATACTCACTTTTGATAATCCTTGTATTTCTATAGGAGACAGGGCAGAA	p.Asp385fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 9 of 9	ENST00000383791.8	NP_004835.2	O60239-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3BP5	ENST00000383791.8 link	c.1151-40_1164delTTGTCAATACTCACTTTTGATAATCCTTGTATTTCTATAGGAGACAGGGCAGAA	p.Asp385fs	frameshift_variant, splice_acceptor_variant, splice_region_variant, intron_variant	Exon 9 of 9	1	NM_004844.5	ENSP00000373301.3		O60239-1

Frequencies

GnomAD3 genomes

AF:

0.00238

AC:

362

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00831

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000588

Gnomad OTH

AF:

0.00144

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000300

AC:

438

AN:

1461804

Hom.:

AF XY:

0.000285

AC XY:

207

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.00996

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000468

Gnomad4 OTH exome

AF:

0.000530

GnomAD4 genome

AF:

0.00239

AC:

364

AN:

152270

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

183

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.00833

Gnomad4 AMR

AF:

0.000719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00111

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 08, 2018

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

Splicing

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