Genetic Variant UBA1:c.811+9C>G (chrX-47201619-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_003334.4(UBA1):c.811+9C>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 0.99 ( 37872 hom., 32775 hem., cov: 23)

Exomes 𝑓: 0.98 ( 355394 hom. 356236 hem. )

Failed GnomAD Quality Control

Consequence

UBA1
NM_003334.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.363

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant X-47201619-C-G is Benign according to our data. Variant chrX-47201619-C-G is described in ClinVar as [Benign]. Clinvar id is 368331.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-47201619-C-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA1	NM_003334.4 link	c.811+9C>G		intron_variant	Intron 8 of 25	ENST00000335972.11	NP_003325.2	P22314-1A0A024R1A3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBA1	ENST00000335972.11 link	c.811+9C>G	intron_variant	Intron 8 of 25	1	NM_003334.4	ENSP00000338413.6	P22314-1
UBA1	ENST00000377351.8 link	c.811+9C>G	intron_variant	Intron 8 of 25	1		ENSP00000366568.4	P22314-1
UBA1	ENST00000442035.5 link	c.*9C>G	downstream_gene_variant		5		ENSP00000389583.1	Q5JRS0
UBA1	ENST00000412206.5 link	c.*8C>G	downstream_gene_variant		5		ENSP00000415033.1	Q5JRR9

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

109502

AN:

111040

Hom.:

37880

Cov.:

AF XY:

0.986

AC XY:

32711

AN XY:

33192

FAILED QC

Gnomad AFR

AF:

0.997

Gnomad AMI

AF:

0.909

Gnomad AMR

AF:

0.990

Gnomad ASJ

AF:

0.980

Gnomad EAS

AF:

0.953

Gnomad SAS

AF:

0.934

Gnomad FIN

AF:

0.996

Gnomad MID

AF:

0.987

Gnomad NFE

AF:

0.984

Gnomad OTH

AF:

0.983

GnomAD3 exomes

AF:

0.980

AC:

178301

AN:

182014

Hom.:

55551

AF XY:

0.976

AC XY:

65197

AN XY:

66816

show subpopulations

Gnomad AFR exome

AF:

0.998

Gnomad AMR exome

AF:

0.993

Gnomad ASJ exome

AF:

0.981

Gnomad EAS exome

AF:

0.953

Gnomad SAS exome

AF:

0.933

Gnomad FIN exome

AF:

0.995

Gnomad NFE exome

AF:

0.984

Gnomad OTH exome

AF:

0.978

GnomAD4 exome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.983

AC:

1078778

AN:

1097948

Hom.:

355394

Cov.:

AF XY:

0.980

AC XY:

356236

AN XY:

363330

show subpopulations

Gnomad4 AFR exome

AF:

0.998

Gnomad4 AMR exome

AF:

0.992

Gnomad4 ASJ exome

AF:

0.982

Gnomad4 EAS exome

AF:

0.972

Gnomad4 SAS exome

AF:

0.934

Gnomad4 FIN exome

AF:

0.994

Gnomad4 NFE exome

AF:

0.985

Gnomad4 OTH exome

AF:

0.979

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.986

AC:

109552

AN:

111094

Hom.:

37872

Cov.:

AF XY:

0.986

AC XY:

32775

AN XY:

33256

show subpopulations

Gnomad4 AFR

AF:

0.997

Gnomad4 AMR

AF:

0.990

Gnomad4 ASJ

AF:

0.980

Gnomad4 EAS

AF:

0.953

Gnomad4 SAS

AF:

0.935

Gnomad4 FIN

AF:

0.996

Gnomad4 NFE

AF:

0.984

Gnomad4 OTH

AF:

0.978

Alfa

AF:

0.980

Hom.:

8268

Bravo

AF:

0.987

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Infantile-onset X-linked spinal muscular atrophy

Benign:4

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:3

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 05, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 98% of patients studied by a panel of primary immunodeficiencies. Number of patients: 93. Only high quality variants are reported. -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 16, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.7

DANN

Benign

0.50

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