11-122776228-C-G

Position:

• chr11-122776228-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_001363365.2(UBASH3B):​c.62C>G​(p.Pro21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,610,398 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (17 hom.)
• Consequence: UBASH3B NM_001363365.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.233

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 11-122776228-C-G is Benign according to our data. Variant chr11-122776228-C-G is described in ClinVar as [Benign]. Clinvar id is 774816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 465 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBASH3B	NM_032873.5	c.171C>G	p.Ala57Ala	synonymous_variant	2/14	ENST00000284273.6	NP_116262.2
UBASH3B	NM_001363365.2	c.62C>G	p.Pro21Arg	missense_variant	2/14		NP_001350294.1
UBASH3B	XM_011543041.3	c.110C>G	p.Pro37Arg	missense_variant	2/14		XP_011541343.1
UBASH3B	XM_005271712.4	c.255C>G	p.Ala85Ala	synonymous_variant	2/14		XP_005271769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBASH3B	ENST00000284273.6	c.171C>G	p.Ala57Ala	synonymous_variant	2/14	1	NM_032873.5	ENSP00000284273.5

Frequencies

GnomAD3 genomes AF: 0.00306 AC: 465 AN: 152164 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00242

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.00471

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00484

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00277 AC: 684 AN: 247148 Hom.: 2 AF XY: 0.00286 AC XY: 383 AN XY: 133770

Gnomad AFR exome AF: 0.000867

Gnomad AMR exome AF: 0.00125

Gnomad ASJ exome AF: 0.00391

Gnomad EAS exome AF: 0.0000553

Gnomad SAS exome AF: 0.00233

Gnomad FIN exome AF: 0.00463

Gnomad NFE exome AF: 0.00351

Gnomad OTH exome AF: 0.00402

GnomAD4 exome AF: 0.00363 AC: 5290 AN: 1458116 Hom.: 17 Cov.: 29 AF XY: 0.00362 AC XY: 2624 AN XY: 725464

Gnomad4 AFR exome AF: 0.000571

Gnomad4 AMR exome AF: 0.00131

Gnomad4 ASJ exome AF: 0.00395

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00237

Gnomad4 FIN exome AF: 0.00498

Gnomad4 NFE exome AF: 0.00393

Gnomad4 OTH exome AF: 0.00395

GnomAD4 genome AF: 0.00305 AC: 465 AN: 152282 Hom.: 2 Cov.: 32 AF XY: 0.00283 AC XY: 211 AN XY: 74458

Gnomad4 AFR AF: 0.000530

Gnomad4 AMR AF: 0.00242

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00471

Gnomad4 NFE AF: 0.00484

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00449 Hom.: 0

Bravo AF: 0.00247

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	10
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs34347341; hg19: chr11-122646936;