11-122796180-G-A

Position:

chr11-122796180-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_032873.5(UBASH3B):c.1138G>A(p.Gly380Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00119 in 1,614,048 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0063 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00065 ( 7 hom. )

Consequence

UBASH3B
NM_032873.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.28

Variant links:

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]

UBASH3B links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002783209).

BP6

Variant 11-122796180-G-A is Benign according to our data. Variant chr11-122796180-G-A is described in ClinVar as [Benign]. Clinvar id is 711917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00633 (964/152222) while in subpopulation AFR AF= 0.0218 (907/41542). AF 95% confidence interval is 0.0207. There are 13 homozygotes in gnomad4. There are 463 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 964 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
UBASH3B	NM_032873.5 linkuse as main transcript	c.1138G>A	p.Gly380Ser	missense_variant	8/14	ENST00000284273.6
UBASH3B	NM_001363365.2 linkuse as main transcript	c.1033G>A	p.Gly345Ser	missense_variant	8/14
UBASH3B	XM_005271712.4 linkuse as main transcript	c.1222G>A	p.Gly408Ser	missense_variant	8/14
UBASH3B	XM_011543041.3 linkuse as main transcript	c.1081G>A	p.Gly361Ser	missense_variant	8/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
UBASH3B	ENST00000284273.6 linkuse as main transcript	c.1138G>A	p.Gly380Ser	missense_variant	8/14	1	NM_032873.5	P1
	ENST00000649590.1 linkuse as main transcript	n.74-30131C>T		intron_variant, non_coding_transcript_variant
UBASH3B	ENST00000530578.1 linkuse as main transcript	n.82G>A		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes

AF:

0.00632

AC:

962

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00150

AC:

376

AN:

251330

Hom.:

AF XY:

0.00107

AC XY:

146

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.0211

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000704

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000650

AC:

950

AN:

1461826

Hom.:

Cov.:

AF XY:

0.000535

AC XY:

389

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0230

Gnomad4 AMR exome

AF:

0.00132

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000360

Gnomad4 OTH exome

AF:

0.00124

GnomAD4 genome

AF:

0.00633

AC:

964

AN:

152222

Hom.:

Cov.:

AF XY:

0.00622

AC XY:

463

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0218

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00522

Alfa

AF:

0.00116

Hom.:

Bravo

AF:

0.00713

ESP6500AA

AF:

0.0182

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00202

AC:

245

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

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	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.021

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.061

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.85

MetaRNN

Benign

0.0028

MetaSVM

Benign

-0.88

MutationAssessor

Benign

0.71

MutationTaster

Benign

0.95

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.53

REVEL

Benign

0.028

Sift

Benign

0.88

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.29

MVP

0.068

MPC

0.48

ClinPred

0.018

GERP RS

4.6

Varity_R

0.050

gMVP

0.15

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over