Variant 3-179653241-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003940.3(USP13):c.16G>T(p.Ala6Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000677 in 1,550,472 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 1 hom. )

Consequence

USP13
NM_003940.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

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:

ENSG00000288698 (HGNC:):

ENSG00000288698 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2642569).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
USP13	NM_003940.3 linkuse as main transcript	c.16G>T	p.Ala6Ser	missense_variant	1/21	ENST00000263966.8	NP_003931.2	Q92995-1A0A0A6YZ17
USP13	XM_011513269.2 linkuse as main transcript	c.16G>T	p.Ala6Ser	missense_variant	1/20		XP_011511571.1
USP13	XM_017007426.2 linkuse as main transcript	c.16G>T	p.Ala6Ser	missense_variant	1/20		XP_016862915.1
USP13	XM_047449154.1 linkuse as main transcript	c.16G>T	p.Ala6Ser	missense_variant	1/19		XP_047305110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
USP13	ENST00000263966.8 linkuse as main transcript	c.16G>T	p.Ala6Ser	missense_variant	1/21	1	NM_003940.3	ENSP00000263966.3		Q92995-1
ENSG00000288698	ENST00000680408.1 linkuse as main transcript	n.*383+12385G>T		intron_variant				ENSP00000506198.1		A0A7P0TAR2

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151458

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000657

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000715

AC:

100

AN:

1399014

Hom.:

Cov.:

AF XY:

0.0000637

AC XY:

AN XY:

690522

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000879

Gnomad4 OTH exome

AF:

0.0000862

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151458

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73942

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000591

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000853

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000123

AC:

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

Jan 18, 2022

The c.16G>T (p.A6S) alteration is located in exon 1 (coding exon 1) of the USP13 gene. This alteration results from a G to T substitution at nucleotide position 16, causing the alanine (A) at amino acid position 6 to be replaced by a serine (S). 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

0.11

BayesDel_addAF

Benign

-0.089

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.026

Eigen

Benign

-0.14

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.26

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.16

REVEL

Benign

0.076

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.68

Vest4

0.25

MVP

0.36

MPC

0.27

ClinPred

0.63

GERP RS

2.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.28

gMVP

0.51

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