Genetic Variant UBASH3B:p.Ala57Ala (chr11-122776228-C-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.233

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:

ENSG00000285909 (HGNC:):

ENSG00000285909 links:

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ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
UBASH3B	NM_032873.5 link	c.171C>G	p.Ala57Ala	synonymous_variant	Exon 2 of 14	ENST00000284273.6	NP_116262.2	Q8TF42
UBASH3B	NM_001363365.2 link	c.62C>G	p.Pro21Arg	missense_variant	Exon 2 of 14		NP_001350294.1
UBASH3B	XM_011543041.3 link	c.110C>G	p.Pro37Arg	missense_variant	Exon 2 of 14		XP_011541343.1
UBASH3B	XM_005271712.4 link	c.255C>G	p.Ala85Ala	synonymous_variant	Exon 2 of 14		XP_005271769.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBASH3B	ENST00000284273.6 link	c.171C>G	p.Ala57Ala	synonymous_variant	Exon 2 of 14	1	NM_032873.5	ENSP00000284273.5		Q8TF42

Frequencies

GnomAD3 genomes

AF:

0.00306

AC:

465

AN:

152164

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00286

AC XY:

383

AN XY:

133770

show subpopulations

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.:

Cov.:

AF XY:

0.00362

AC XY:

2624

AN XY:

725464

show subpopulations

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.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74458

show subpopulations

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.:

Bravo

AF:

0.00247

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 04, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

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

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