Variant 1-202334996-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014176.4(UBE2T):c.172C>G(p.Pro58Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000554 in 1,612,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00058 ( 0 hom. )

Consequence

UBE2T
NM_014176.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.16

Variant links:

Genes affected

UBE2T (HGNC:25009): (ubiquitin conjugating enzyme E2 T) The protein encoded by this gene catalyzes the covalent attachment of ubiquitin to protein substrates. Defects in this gene have been associated with Fanconi anemia of complementation group T. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

UBE2T links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2T	NM_014176.4 linkuse as main transcript	c.172C>G	p.Pro58Ala	missense_variant	3/7	ENST00000646651.1	NP_054895.1
UBE2T	NM_001310326.2 linkuse as main transcript	c.82C>G	p.Pro28Ala	missense_variant	3/7		NP_001297255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2T	ENST00000646651.1 linkuse as main transcript	c.172C>G	p.Pro58Ala	missense_variant	3/7		NM_014176.4	ENSP00000494957	P3

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000647

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000302

AC:

AN:

248664

Hom.:

AF XY:

0.000298

AC XY:

AN XY:

134370

show subpopulations

Gnomad AFR exome

AF:

0.0000634

Gnomad AMR exome

AF:

0.0000874

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:

0.000622

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000580

AC:

847

AN:

1460176

Hom.:

Cov.:

AF XY:

0.000560

AC XY:

407

AN XY:

726194

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000449

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000733

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000302

AC:

AN:

152242

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000463

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000371

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 04, 2022

This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 58 of the UBE2T protein (p.Pro58Ala). This variant is present in population databases (rs147122531, gnomAD 0.06%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with UBE2T-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

T;T

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.98

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.93

.;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Uncertain

0.11

MutationAssessor

Pathogenic

4.1

H;H

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-7.3

.;D

REVEL

Uncertain

0.55

Sift

Uncertain

0.014

.;D

Sift4G

Uncertain

0.010

.;D

Polyphen

0.99

D;D

Vest4

0.79

MVP

0.92

MPC

0.50

ClinPred

0.72

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Varity_R

0.94

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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