rs955051

chr11-122789210-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_032873.5(UBASH3B):c.882T>G(p.Gly294=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,613,960 control chromosomes in the GnomAD database, including 20,100 homozygotes. 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 0.12 (1356 hom., cov: 32)
  • Exomes 𝑓: 0.15 (18744 hom.)
• Consequence: UBASH3B NM_032873.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

Genes affected

UBASH3B (HGNC:29884): (ubiquitin associated and SH3 domain containing B) This gene encodes a protein that contains a ubiquitin associated domain at the N-terminus, an SH3 domain, and a C-terminal domain with similarities to the catalytic motif of phosphoglycerate mutase. The encoded protein was found to inhibit endocytosis of epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=1.17 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBASH3B	NM_032873.5	c.882T>G	p.Gly294=	synonymous_variant	6/14	ENST00000284273.6
UBASH3B	NM_001363365.2	c.777T>G	p.Gly259=	synonymous_variant	6/14
UBASH3B	XM_005271712.4	c.966T>G	p.Gly322=	synonymous_variant	6/14
UBASH3B	XM_011543041.3	c.825T>G	p.Gly275=	synonymous_variant	6/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBASH3B	ENST00000284273.6	c.882T>G	p.Gly294=	synonymous_variant	6/14	1	NM_032873.5	P1
	ENST00000649590.1	n.74-23161A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18118 AN: 151986 Hom.: 1361 Cov.: 32

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.0658

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.0369

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.0668

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.143

GnomAD3 exomes AF: 0.135 AC: 33998 AN: 251328 Hom.: 2858 AF XY: 0.144 AC XY: 19498 AN XY: 135830

Gnomad AFR exome AF: 0.0437

Gnomad AMR exome AF: 0.0762

Gnomad ASJ exome AF: 0.264

Gnomad EAS exome AF: 0.0406

Gnomad SAS exome AF: 0.188

Gnomad FIN exome AF: 0.0724

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.154 AC: 225019 AN: 1461856 Hom.: 18744 Cov.: 33 AF XY: 0.156 AC XY: 113623 AN XY: 727228

Gnomad4 AFR exome AF: 0.0452

Gnomad4 AMR exome AF: 0.0823

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.0332

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.0745

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.156

GnomAD4 genome AF: 0.119 AC: 18110 AN: 152104 Hom.: 1356 Cov.: 32 AF XY: 0.115 AC XY: 8561 AN XY: 74340

Gnomad4 AFR AF: 0.0473

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.0370

Gnomad4 SAS AF: 0.181

Gnomad4 FIN AF: 0.0668

Gnomad4 NFE AF: 0.168

Gnomad4 OTH AF: 0.142

Alfa AF: 0.165 Hom.: 3766

Bravo AF: 0.116

Asia WGS AF: 0.103 AC: 360 AN: 3478

EpiCase AF: 0.182

EpiControl AF: 0.180

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	10
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs955051; hg19: chr11-122659918; COSMIC: COSV52492037;