Variant chrX-47198248-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_003334.4(UBA1):c.1-555A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 1.0 ( 38822 hom., 31759 hem., cov: 22)

Exomes 𝑓: 1.0 ( 293335 hom. 282199 hem. )

Failed GnomAD Quality Control

Consequence

UBA1
NM_003334.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.641

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2715918E-6).

BP6

Variant X-47198248-A-G is Benign according to our data. Variant chrX-47198248-A-G is described in ClinVar as [Benign]. Clinvar id is 2688098.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-47198248-A-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
UBA1	NM_003334.4 linkuse as main transcript	c.1-555A>G		intron_variant		ENST00000335972.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
UBA1	ENST00000335972.11 linkuse as main transcript	c.1-555A>G		intron_variant		1	NM_003334.4	P1	P22314-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

109431

AN:

109546

Hom.:

38827

Cov.:

AF XY:

0.999

AC XY:

31697

AN XY:

31732

FAILED QC

Gnomad AFR

AF:

0.999

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

1.00

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

0.975

Gnomad SAS

AF:

0.999

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.999

GnomAD3 exomes

AF:

0.998

AC:

108363

AN:

108573

Hom.:

34279

AF XY:

0.998

AC XY:

39674

AN XY:

39747

show subpopulations

Gnomad AFR exome

AF:

0.999

Gnomad AMR exome

AF:

1.00

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

0.975

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

1.00

AC:

869089

AN:

869411

Hom.:

293335

Cov.:

AF XY:

1.00

AC XY:

282199

AN XY:

282297

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

0.975

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.999

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.999

AC:

109483

AN:

109598

Hom.:

38822

Cov.:

AF XY:

0.999

AC XY:

31759

AN XY:

31794

show subpopulations

Gnomad4 AFR

AF:

0.999

Gnomad4 AMR

AF:

1.00

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

0.975

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.999

Alfa

AF:

1.00

Hom.:

8786

Bravo

AF:

0.999

TwinsUK

AF:

1.00

AC:

3708

ALSPAC

AF:

1.00

AC:

2889

ExAC

AF:

0.999

AC:

18883

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.086

DANN

Benign

0.20

DEOGEN2

Benign

0.011

T;.

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.20

T;T

MetaRNN

Benign

0.0000013

T;T

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

P;P

PROVEAN

Benign

0.010

N;N

REVEL

Benign

0.084

Sift

Pathogenic

0.0

D;D

ClinPred

0.0023

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.8

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