11-122776228-C-G

Variant names:

• chr11-122776228-C-G
• rs34347341
• NM_032873.5:c.171C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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 -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 VariationId is 774816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 465 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363365.2. 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.171C>G	p.Ala57Ala	synonymous	Exon 2 of 14	NP_116262.2
	UBASH3B	NM_001363365.2		c.62C>G	p.Pro21Arg	missense	Exon 2 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.171C>G	p.Ala57Ala	synonymous	Exon 2 of 14	ENSP00000284273.5	Q8TF42
	UBASH3B	ENST00000526386.5	TSL:4	n.223C>G		non_coding_transcript_exon	Exon 2 of 4
	UBASH3B	ENST00000530917.5	TSL:5	n.178C>G		non_coding_transcript_exon	Exon 2 of 6

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

GnomAD2 exomes AF: 0.00277 AC: 684 AN: 247148 AF XY: 0.00286

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 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

African (AFR) AF: 0.000571 AC: 19 AN: 33294

American (AMR) AF: 0.00131 AC: 57 AN: 43568

Ashkenazi Jewish (ASJ) AF: 0.00395 AC: 103 AN: 26052

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39518

South Asian (SAS) AF: 0.00237 AC: 203 AN: 85666

European-Finnish (FIN) AF: 0.00498 AC: 266 AN: 53376

Middle Eastern (MID) AF: 0.00660 AC: 38 AN: 5756

European-Non Finnish (NFE) AF: 0.00393 AC: 4365 AN: 1110660

Other (OTH) AF: 0.00395 AC: 238 AN: 60226

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

African (AFR) AF: 0.000530 AC: 22 AN: 41542

American (AMR) AF: 0.00242 AC: 37 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4820

European-Finnish (FIN) AF: 0.00471 AC: 50 AN: 10612

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00484 AC: 329 AN: 68034

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00449 Hom.: 0

Bravo AF: 0.00247

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	-0.31
CADD	Benign	10
DANN	Benign	0.72
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34347341; hg19: chr11-122646936;