rs774357609

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_014176.4(UBE2T):c.4C>G(p.Gln2Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

UBE2T
NM_014176.4 missense

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:3

Conservation

PhyloP100: 9.25

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

Fanconi anemia complementation group T
Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

UBE2T links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-202335751-G-C is Pathogenic according to our data. Variant chr1-202335751-G-C is described in ClinVar as Pathogenic. ClinVar VariationId is 199436.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBE2T	NM_014176.4 link	c.4C>G	p.Gln2Glu	missense_variant	Exon 2 of 7	ENST00000646651.1	NP_054895.1	Q9NPD8A0A024R9A9
UBE2T	NM_001310326.2 link	c.-91C>G		5_prime_UTR_variant	Exon 2 of 7		NP_001297255.1	Q9NPD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBE2T	ENST00000646651.1 link	c.4C>G	p.Gln2Glu	missense_variant	Exon 2 of 7		NM_014176.4	ENSP00000494957.1		Q9NPD8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249478

AF XY:

0.00000741

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727112

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.000101

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111852

Other (OTH)

AF:

0.00

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Fanconi anemia complementation group T

Pathogenic:3

Mar 20, 2020

Revvity Omics, Revvity

Significance:Pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 04, 2015

OMIM

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Jul 19, 2015

Leiden Open Variation Database

Significance:Pathogenic

Review Status:no assertion criteria provided

Collection Method:curation

Curator: Arleen D. Auerbach. Submitter to LOVD: Johan den Dunnen. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

T;T

Eigen

Pathogenic

0.79

Eigen_PC

Pathogenic

0.82

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.87

.;D

M_CAP

Benign

0.010

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.65

MutationAssessor

Pathogenic

3.2

M;M

PhyloP100

9.3

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-1.6

.;N

REVEL

Benign

0.15

Sift

Uncertain

0.0090

.;D

Sift4G

Uncertain

0.049

.;D

Polyphen

0.98

D;D

Vest4

0.91

MutPred

0.29

Loss of MoRF binding (P = 0.102);Loss of MoRF binding (P = 0.102);

MVP

0.75

MPC

0.68

ClinPred

0.77

GERP RS

6.0

Varity_R

0.75

gMVP

0.70

Mutation Taster

=30/70

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over