Variant 19-34428463-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_005499.3(UBA2):c.31C>A(p.Leu11Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,118 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBA2
NM_005499.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

Variant links:

Genes affected

UBA2 (HGNC:30661): (ubiquitin like modifier activating enzyme 2) Posttranslational modification of proteins by the addition of the small protein SUMO (see SUMO1; MIM 601912), or sumoylation, regulates protein structure and intracellular localization. SAE1 (MIM 613294) and UBA2 form a heterodimer that functions as a SUMO-activating enzyme for the sumoylation of proteins (Okuma et al., 1999 [PubMed 9920803]).[supplied by OMIM, Mar 2010]

UBA2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, UBA2

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBA2	NM_005499.3 linkuse as main transcript	c.31C>A	p.Leu11Met	missense_variant	1/17	ENST00000246548.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBA2	ENST00000246548.9 linkuse as main transcript	c.31C>A	p.Leu11Met	missense_variant	1/17	1	NM_005499.3	P1	Q9UBT2-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1134250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

540722

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

AF:

0.00000657

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

The c.31C>A (p.L11M) alteration is located in exon 1 (coding exon 1) of the UBA2 gene. This alteration results from a C to A substitution at nucleotide position 31, causing the leucine (L) at amino acid position 11 to be replaced by a methionine (M). 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

0.19

BayesDel_addAF

Uncertain

0.097

BayesDel_noAF

Benign

-0.10

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.31

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.80

N;.

REVEL

Benign

0.25

Sift

Uncertain

0.010

D;.

Sift4G

Uncertain

0.024

D;D

Polyphen

0.99

D;.

Vest4

0.37

MutPred

0.52

Gain of MoRF binding (P = 0.0726);Gain of MoRF binding (P = 0.0726);

MVP

0.63

MPC

1.6

ClinPred

0.90

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.80

gMVP

0.26

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