rs150574055

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003334.4(UBA1):c.1702C>G(p.Leu568Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00351 in 1,203,705 control chromosomes in the GnomAD database, including 55 homozygotes. There are 1,397 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0041 ( 4 hom., 172 hem., cov: 24)

Exomes 𝑓: 0.0035 ( 51 hom. 1225 hem. )

Consequence

UBA1
NM_003334.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.09

Publications

8 publications found

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:

INE1 (HGNC:6060): (inactivation escape 1) X chromosome inactivation provides dosage compensation for the expression level of X-linked genes from the single X in males and the two in females. This X chromosome gene is intronless and was identified because its transcription escapes X inactivation in females. This gene does not make a protein.[provided by RefSeq, May 2010]

INE1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_003334.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008150339).

BP6

Variant X-47206074-C-G is Benign according to our data. Variant chrX-47206074-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 368339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003334.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
UBA1	NM_003334.4	MANE Select	c.1702C>G	p.Leu568Val	missense	Exon 15 of 26	NP_003325.2
UBA1	NM_001440807.1		c.1744C>G	p.Leu582Val	missense	Exon 16 of 27	NP_001427736.1
UBA1	NM_001440809.1		c.1720C>G	p.Leu574Val	missense	Exon 16 of 27	NP_001427738.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBA1	ENST00000335972.11	TSL:1 MANE Select	c.1702C>G	p.Leu568Val	missense	Exon 15 of 26	ENSP00000338413.6	P22314-1
UBA1	ENST00000377351.8	TSL:1	c.1702C>G	p.Leu568Val	missense	Exon 15 of 26	ENSP00000366568.4	P22314-1
UBA1	ENST00000880189.1		c.1837C>G	p.Leu613Val	missense	Exon 16 of 27	ENSP00000550248.1

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

458

AN:

111825

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000188

Gnomad ASJ

AF:

0.0106

Gnomad EAS

AF:

0.0556

Gnomad SAS

AF:

0.00417

Gnomad FIN

AF:

0.0253

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000941

Gnomad OTH

AF:

0.00403

GnomAD2 exomes

AF:

0.00782

AC:

1306

AN:

167034

AF XY:

0.00702

show subpopulations

Gnomad AFR exome

AF:

0.000167

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00700

Gnomad EAS exome

AF:

0.0548

Gnomad FIN exome

AF:

0.0240

Gnomad NFE exome

AF:

0.00146

Gnomad OTH exome

AF:

0.00878

GnomAD4 exome

AF:

0.00345

AC:

3772

AN:

1091826

Hom.:

Cov.:

AF XY:

0.00342

AC XY:

1225

AN XY:

358234

show subpopulations

African (AFR)

AF:

0.0000761

AC:

AN:

26282

American (AMR)

AF:

0.0000290

AC:

AN:

34541

Ashkenazi Jewish (ASJ)

AF:

0.00684

AC:

132

AN:

19305

East Asian (EAS)

AF:

0.0632

AC:

1890

AN:

29919

South Asian (SAS)

AF:

0.00318

AC:

168

AN:

52909

European-Finnish (FIN)

AF:

0.0239

AC:

956

AN:

40076

Middle Eastern (MID)

AF:

0.000726

AC:

AN:

4134

European-Non Finnish (NFE)

AF:

0.000484

AC:

406

AN:

838824

Other (OTH)

AF:

0.00467

AC:

214

AN:

45836

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

190

381

571

762

952

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00408

AC:

456

AN:

111879

Hom.:

Cov.:

AF XY:

0.00505

AC XY:

172

AN XY:

34075

show subpopulations

African (AFR)

AF:

0.000325

AC:

AN:

30811

American (AMR)

AF:

0.000188

AC:

AN:

10629

Ashkenazi Jewish (ASJ)

AF:

0.0106

AC:

AN:

2650

East Asian (EAS)

AF:

0.0553

AC:

195

AN:

3529

South Asian (SAS)

AF:

0.00418

AC:

AN:

2631

European-Finnish (FIN)

AF:

0.0253

AC:

154

AN:

6097

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.000941

AC:

AN:

53121

Other (OTH)

AF:

0.00398

AC:

AN:

1508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00324

Hom.:

Bravo

AF:

0.00297

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

Infantile-onset X-linked spinal muscular atrophy (2)

Infantile-onset X-linked spinal muscular atrophy;C5435753:VEXAS syndrome (1)

not provided (1)

UBA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0082

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.8

PhyloP100

2.1

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.39

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.040

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.91

gMVP

0.94

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over