Variant 3-179653286-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003940.3(USP13):c.61G>A(p.Ala21Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000165 in 1,571,746 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

USP13
NM_003940.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.05

Variant links:

Genes affected

USP13 (HGNC:12611): (ubiquitin specific peptidase 13) Enables several functions, including BAT3 complex binding activity; chaperone binding activity; and cysteine-type peptidase activity. Involved in several processes, including maintenance of unfolded protein involved in ERAD pathway; regulation of cellular catabolic process; and regulation of transcription, DNA-templated. Acts upstream of or within protein deubiquitination and protein stabilization. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

USP13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14473322).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
USP13	NM_003940.3 linkuse as main transcript	c.61G>A	p.Ala21Thr	missense_variant	1/21	ENST00000263966.8
USP13	XM_011513269.2 linkuse as main transcript	c.61G>A	p.Ala21Thr	missense_variant	1/20
USP13	XM_017007426.2 linkuse as main transcript	c.61G>A	p.Ala21Thr	missense_variant	1/20
USP13	XM_047449154.1 linkuse as main transcript	c.61G>A	p.Ala21Thr	missense_variant	1/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USP13	ENST00000263966.8 linkuse as main transcript	c.61G>A	p.Ala21Thr	missense_variant	1/21	1	NM_003940.3	P4	Q92995-1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000220

AC:

AN:

182072

Hom.:

AF XY:

0.0000307

AC XY:

AN XY:

97788

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000288

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000141

AC:

AN:

1419636

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

702304

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000213

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.16e-7

Gnomad4 OTH exome

AF:

0.000187

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000340

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 02, 2023

The c.61G>A (p.A21T) alteration is located in exon 1 (coding exon 1) of the USP13 gene. This alteration results from a G to A substitution at nucleotide position 61, causing the alanine (A) at amino acid position 21 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.40

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Benign

0.017

Eigen_PC

Benign

0.034

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.80

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

0.99

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.42

REVEL

Benign

0.097

Sift

Pathogenic

0.0

Sift4G

Benign

0.16

Polyphen

0.97

Vest4

0.31

MutPred

0.24

Loss of glycosylation at K18 (P = 0.0176);

MVP

0.45

MPC

0.91

ClinPred

0.68

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.57

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