rs35380329

Variant names:

• chr11-122777123-C-T
• rs35380329
• NM_032873.5:c.315C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_032873.5(UBASH3B):​c.315C>T​(p.Ser105Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00389 in 1,614,072 control chromosomes in the GnomAD database, including 219 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (109 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (110 hom.)
• Consequence: UBASH3B NM_032873.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.09
• Publications: 0 publications found

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]

ENSG00000285909 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 11-122777123-C-T is Benign according to our data. Variant chr11-122777123-C-T is described in ClinVar as Benign. ClinVar VariationId is 781236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-6.09 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0703 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032873.5. 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
	UBASH3B	NM_032873.5	MANE Select	c.315C>T	p.Ser105Ser	synonymous	Exon 3 of 14	NP_116262.2
	UBASH3B	NM_001363365.2		c.210C>T	p.Ser70Ser	synonymous	Exon 3 of 14	NP_001350294.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBASH3B	ENST00000284273.6	TSL:1 MANE Select	c.315C>T	p.Ser105Ser	synonymous	Exon 3 of 14	ENSP00000284273.5	Q8TF42
	UBASH3B	ENST00000526386.5	TSL:4	n.367C>T		non_coding_transcript_exon	Exon 3 of 4
	UBASH3B	ENST00000530917.5	TSL:5	n.322C>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes AF: 0.0206 AC: 3137 AN: 152110 Hom.: 109 Cov.: 32

Gnomad AFR AF: 0.0725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00583

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0134

GnomAD2 exomes AF: 0.00530 AC: 1333 AN: 251320 AF XY: 0.00404

Gnomad AFR exome AF: 0.0723

Gnomad AMR exome AF: 0.00347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000211

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.00215 AC: 3136 AN: 1461844 Hom.: 110 Cov.: 30 AF XY: 0.00184 AC XY: 1337 AN XY: 727228

African (AFR) AF: 0.0758 AC: 2537 AN: 33474

American (AMR) AF: 0.00382 AC: 171 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53420

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.000112 AC: 125 AN: 1111984

Other (OTH) AF: 0.00460 AC: 278 AN: 60394

GnomAD4 genome AF: 0.0206 AC: 3143 AN: 152228 Hom.: 109 Cov.: 32 AF XY: 0.0204 AC XY: 1516 AN XY: 74440

African (AFR) AF: 0.0725 AC: 3010 AN: 41530

American (AMR) AF: 0.00582 AC: 89 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68012

Other (OTH) AF: 0.0133 AC: 28 AN: 2112

Alfa AF: 0.00898 Hom.: 19

Bravo AF: 0.0228

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.22
DANN	Benign	0.78
PhyloP100		-6.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs35380329; hg19: chr11-122647831;