Genetic Variant UBA1:p.Leu931Leu (chrX-47213136-G-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003334.4(UBA1):c.2793G>T(p.Leu931Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000984 in 1,209,945 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 37 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000097 ( 0 hom. 34 hem. )

Consequence

UBA1
NM_003334.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.17

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:

LOC105373194 (HGNC:):

LOC105373194 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant X-47213136-G-T is Benign according to our data. Variant chrX-47213136-G-T is described in ClinVar as [Benign]. Clinvar id is 1599564.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.17 with no splicing effect.

BS2

High Hemizygotes in GnomAd4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA1	NM_003334.4 link	c.2793G>T	p.Leu931Leu	synonymous_variant	Exon 23 of 26	ENST00000335972.11	NP_003325.2	P22314-1A0A024R1A3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBA1	ENST00000335972.11 link	c.2793G>T	p.Leu931Leu	synonymous_variant	Exon 23 of 26	1	NM_003334.4	ENSP00000338413.6	P22314-1
UBA1	ENST00000377351.8 link	c.2793G>T	p.Leu931Leu	synonymous_variant	Exon 23 of 26	1		ENSP00000366568.4	P22314-1
UBA1	ENST00000377269.3 link	c.1137G>T	p.Leu379Leu	synonymous_variant	Exon 7 of 10	2		ENSP00000366481.3	Q5JRR6

Frequencies

GnomAD3 genomes

AF:

0.000116

AC:

AN:

111833

Hom.:

Cov.:

AF XY:

0.0000882

AC XY:

AN XY:

33999

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000230

AC:

AN:

182964

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

67472

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00214

Gnomad NFE exome

AF:

0.0000857

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.0000965

AC:

106

AN:

1098112

Hom.:

Cov.:

AF XY:

0.0000935

AC XY:

AN XY:

363480

show subpopulations

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:

0.00195

Gnomad4 NFE exome

AF:

0.0000297

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.000116

AC:

AN:

111833

Hom.:

Cov.:

AF XY:

0.0000882

AC XY:

AN XY:

33999

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Infantile-onset X-linked spinal muscular atrophy

Benign:1

Oct 13, 2022

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.47

CADD

Benign

3.8

DANN

Benign

0.84

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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