Variant X-47199477-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_003334.4(UBA1):c.346-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,210,196 control chromosomes in the GnomAD database, including 2 homozygotes. There are 168 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 2 hom., 73 hem., cov: 23)

Exomes 𝑓: 0.00031 ( 0 hom. 95 hem. )

Consequence

UBA1
NM_003334.4 splice_region, intron

Scores

Splicing: ADA: 0.9916

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.278

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 Benign. Variant got -12 ACMG points.

BP6

Variant X-47199477-C-A is Benign according to our data. Variant chrX-47199477-C-A is described in ClinVar as [Benign]. Clinvar id is 533622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBA1	NM_003334.4 linkuse as main transcript	c.346-3C>A		splice_region_variant, intron_variant		ENST00000335972.11	NP_003325.2	P22314-1A0A024R1A3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBA1	ENST00000335972.11 linkuse as main transcript	c.346-3C>A		splice_region_variant, intron_variant		1	NM_003334.4	ENSP00000338413.6		P22314-1

Frequencies

GnomAD3 genomes

AF:

0.00245

AC:

274

AN:

111888

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

AN XY:

34046

show subpopulations

Gnomad AFR

AF:

0.00850

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000944

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:

0.00200

GnomAD3 exomes

AF:

0.000752

AC:

138

AN:

183493

Hom.:

AF XY:

0.000456

AC XY:

AN XY:

67925

show subpopulations

Gnomad AFR exome

AF:

0.00942

Gnomad AMR exome

AF:

0.000328

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000210

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000312

AC:

343

AN:

1098255

Hom.:

Cov.:

AF XY:

0.000261

AC XY:

AN XY:

363609

show subpopulations

Gnomad4 AFR exome

AF:

0.0112

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.000542

GnomAD4 genome

AF:

0.00247

AC:

276

AN:

111941

Hom.:

Cov.:

AF XY:

0.00214

AC XY:

AN XY:

34109

show subpopulations

Gnomad4 AFR

AF:

0.00855

Gnomad4 AMR

AF:

0.000943

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:

0.00197

Alfa

AF:

0.00250

Hom.:

Bravo

AF:

0.00340

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Infantile-onset X-linked spinal muscular atrophy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.3

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.81

SpliceAI score (max)

0.070

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