Variant chrX-119574743-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3PP5

The NM_003336.4(UBE2A):c.32G>A(p.Arg11Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

UBE2A
NM_003336.4 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 6.16

Variant links:

Genes affected

UBE2A (HGNC:12472): (ubiquitin conjugating enzyme E2 A) The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, ubiquitin-conjugating enzymes, and ubiquitin-protein ligases. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is required for post-replicative DNA damage repair, and may play a role in transcriptional regulation. Mutations in this gene are associated with cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

UBE2A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.765

PP5

Variant X-119574743-G-A is Pathogenic according to our data. Variant chrX-119574743-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 29993.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
UBE2A	NM_003336.4 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	1/6	ENST00000371558.7	NP_003327.2
UBE2A	NM_181762.3 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	1/5		NP_861427.1
UBE2A	NM_001282161.2 linkuse as main transcript	c.-61G>A		5_prime_UTR_variant	1/6		NP_001269090.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2A	ENST00000371558.7 linkuse as main transcript	c.32G>A	p.Arg11Gln	missense_variant	1/6	1	NM_003336.4	ENSP00000360613	P4	P49459-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1082021

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

352945

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Syndromic X-linked intellectual disability Nascimento type

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jun 01, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.84

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

T;.;.;T

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D;D

M_CAP

Pathogenic

0.95

MetaRNN

Pathogenic

0.76

D;D;D;D

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.8

L;.;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.0

D;D;.;.

REVEL

Uncertain

0.50

Sift

Benign

0.13

T;T;.;.

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.97

D;.;.;.

Vest4

0.69

MutPred

0.47

Loss of MoRF binding (P = 0.0443);Loss of MoRF binding (P = 0.0443);Loss of MoRF binding (P = 0.0443);Loss of MoRF binding (P = 0.0443);

MVP

0.98

MPC

1.9

ClinPred

0.97

GERP RS

5.2

Varity_R

0.81

gMVP

0.94

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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