NM_004844.5:c.1151-40_1164delTTGTCAATACTCACTTTTGATAATCCTTGTATTTCTATAGGAGACAGGGCAGAA

Variant names:

• chr3-15256289-CTTCTGCCCTGTCTCCTATAGAAATACAAGGATTATCAAAAGTGAGTATTGACAA-C
• rs1559420847
• NM_004844.5:c.1151-40_1164delTTGTCAATACTCACTTTTGATAATCCTTGTATTTCTATAGGAGACAGGGCAGAA

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

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. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. 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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.90
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -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 VariationId is 735908.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004844.5. 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
	SH3BP5	NM_004844.5	MANE Select	c.1151-40_1164delTTGTCAATACTCACTTTTGATAATCCTTGTATTTCTATAGGAGACAGGGCAGAA	p.Asp385fs	frameshift splice_acceptor splice_region intron	Exon 9 of 9	NP_004835.2	O60239-1
	SH3BP5	NM_001018009.4		c.680-40_693delTTGTCAATACTCACTTTTGATAATCCTTGTATTTCTATAGGAGACAGGGCAGAA	p.Asp228fs	frameshift splice_acceptor splice_region intron	Exon 9 of 9	NP_001018009.2	O60239-2
	SH3BP5-AS1	NR_046084.1		n.2135_2188delGGATTATCAAAAGTGAGTATTGACAATTCTGCCCTGTCTCCTATAGAAATACAA		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3BP5	ENST00000383791.8	TSL:1 MANE Select	c.1151-40_1164delTTGTCAATACTCACTTTTGATAATCCTTGTATTTCTATAGGAGACAGGGCAGAA	p.Asp385fs	frameshift splice_acceptor splice_region intron	Exon 9 of 9	ENSP00000373301.3	O60239-1
	SH3BP5	ENST00000408919.7	TSL:1	c.680-40_693delTTGTCAATACTCACTTTTGATAATCCTTGTATTTCTATAGGAGACAGGGCAGAA	p.Asp228fs	frameshift splice_acceptor splice_region intron	Exon 9 of 9	ENSP00000386231.3	O60239-2
	SH3BP5-AS1	ENST00000420195.1	TSL:1	n.2135_2188delGGATTATCAAAAGTGAGTATTGACAATTCTGCCCTGTCTCCTATAGAAATACAA		non_coding_transcript_exon	Exon 1 of 3

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

GnomAD2 exomes AF: 0.000614 AC: 153 AN: 248984 AF XY: 0.000534

Gnomad AFR exome AF: 0.00807

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000808

Gnomad OTH exome AF: 0.000163

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

African (AFR) AF: 0.00996 AC: 333 AN: 33444

American (AMR) AF: 0.000291 AC: 13 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.0000468 AC: 52 AN: 1111978

Other (OTH) AF: 0.000530 AC: 32 AN: 60394

GnomAD4 genome AF: 0.00239 AC: 364 AN: 152270 Hom.: 2 Cov.: 32 AF XY: 0.00246 AC XY: 183 AN XY: 74460

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00833 AC: 346 AN: 41542

American (AMR) AF: 0.000719 AC: 11 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68020

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00111 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.9
Mutation Taster		=16/184	disease causing (long InDel)

Splicing

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

Other links and lift over

dbSNP: rs1559420847; hg19: chr3-15297796;