Variant X-47198883-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_003334.4(UBA1):c.81G>C(p.Gln27His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 112,371 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

UBA1
NM_003334.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.36

Variant links:

Genes affected

UBA1 (HGNC:12469): (ubiquitin like modifier activating enzyme 1) The protein encoded by this gene catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation. This gene complements an X-linked mouse temperature-sensitive defect in DNA synthesis, and thus may function in DNA repair. It is part of a gene cluster on chromosome Xp11.23. Alternatively spliced transcript variants that encode the same protein have been described. [provided by RefSeq, Jul 2008]

UBA1 links:

Genome browser will be placed here

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;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), UBA1. . Gene score misZ 3.4752 (greater than the threshold 3.09). GenCC has associacion of gene with infantile-onset X-linked spinal muscular atrophy, inflammatory disease.

BP4

Computational evidence support a benign effect (MetaRNN=0.07815507).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBA1	NM_003334.4 linkuse as main transcript	c.81G>C	p.Gln27His	missense_variant	2/26	ENST00000335972.11	NP_003325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBA1	ENST00000335972.11 linkuse as main transcript	c.81G>C	p.Gln27His	missense_variant	2/26	1	NM_003334.4	ENSP00000338413	P1	P22314-1

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112371

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34507

show subpopulations

Gnomad AFR

AF:

0.0000324

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112371

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34507

show subpopulations

Gnomad4 AFR

AF:

0.0000324

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:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

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

GeneDx

Jul 18, 2022

Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.47

CADD

Benign

9.9

DANN

Uncertain

0.98

DEOGEN2

Benign

0.069

T;.;T;T;T;T;.

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.52

T;T;T;T;T;.;T

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.078

T;T;T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.69

N;.;.;.;.;N;.

MutationTaster

Benign

0.99

N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

0.020

N;N;N;N;N;N;N

REVEL

Benign

0.15

Sift

Benign

0.76

T;T;T;T;T;T;T

Sift4G

Benign

0.22

T;T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;B;.

Vest4

0.13

MutPred

0.15

Loss of loop (P = 0.0986);Loss of loop (P = 0.0986);.;.;.;Loss of loop (P = 0.0986);.;

MVP

0.27

MPC

0.43

ClinPred

0.32

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.045

gMVP

0.58

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