chr3-15256289-CTTCTGCCCTGTCTCCTATAGAAATACAAGGATTATCAAAAGTGAGTATTGACAA-C

Position:

• chr3-15256289-CTTCTGCCCTGTCTCCTATAGAAATACAAGGATTATCAAAAGTGAGTATTGACAA-C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004844.5(SH3BP5):​c.1151-40_1164del variant causes a splice acceptor, coding sequence, 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 splice_acceptor, coding_sequence, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.90

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

ACMG classification

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/exons	MANE	UniProt
SH3BP5	NM_004844.5	c.1151-40_1164del		splice_acceptor_variant, coding_sequence_variant, intron_variant	9/9	ENST00000383791.8
SH3BP5-AS1	NR_046084.1	n.2135_2188del		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3BP5	ENST00000383791.8	c.1151-40_1164del		splice_acceptor_variant, coding_sequence_variant, intron_variant	9/9	1	NM_004844.5	P1
SH3BP5-AS1	ENST00000420195.1	n.2135_2188del		non_coding_transcript_exon_variant	1/3	1

Frequencies

GnomAD3 genomes AF: 0.00238 AC: 362 AN: 152152 Hom.: 2 Cov.: 32

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.: 3 AF XY: 0.000285 AC XY: 207 AN XY: 727206

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.: 2 Cov.: 32 AF XY: 0.00246 AC XY: 183 AN XY: 74460

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Aug 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1559420847; hg19: chr3-15297796;