rs2230147

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003334.4(UBA1):c.2220G>A(p.Pro740Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,209,034 control chromosomes in the GnomAD database, including 1,785 homozygotes. There are 5,067 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.082 ( 923 hom., 2445 hem., cov: 22)

Exomes 𝑓: 0.0087 ( 862 hom. 2622 hem. )

Consequence

UBA1
NM_003334.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -3.28

Publications

3 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 Gene-Disease associations (from GenCC):

infantile-onset X-linked spinal muscular atrophy
Inheritance: XL Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
inflammatory disease
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

UBA1 links:

LOC105373194 (HGNC:):

LOC105373194 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-47210862-G-A is Benign according to our data. Variant chrX-47210862-G-A is described in ClinVar as [Benign]. Clinvar id is 368342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA1	NM_003334.4 link	c.2220G>A	p.Pro740Pro	synonymous_variant	Exon 19 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.2220G>A	p.Pro740Pro	synonymous_variant	Exon 19 of 26	1	NM_003334.4	ENSP00000338413.6	P22314-1
UBA1	ENST00000377351.8 link	c.2220G>A	p.Pro740Pro	synonymous_variant	Exon 19 of 26	1		ENSP00000366568.4	P22314-1
UBA1	ENST00000377269.3 link	c.564G>A	p.Pro188Pro	synonymous_variant	Exon 3 of 10	2		ENSP00000366481.3	Q5JRR6

Frequencies

GnomAD3 genomes

AF:

0.0812

AC:

9036

AN:

111280

Hom.:

917

Cov.:

show subpopulations

Gnomad AFR

AF:

0.281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0332

Gnomad ASJ

AF:

0.00302

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000745

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0212

Gnomad NFE

AF:

0.000980

Gnomad OTH

AF:

0.0656

GnomAD2 exomes

AF:

0.0229

AC:

4140

AN:

181091

AF XY:

0.0144

show subpopulations

Gnomad AFR exome

AF:

0.282

Gnomad AMR exome

AF:

0.0135

Gnomad ASJ exome

AF:

0.00188

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000706

Gnomad OTH exome

AF:

0.00916

GnomAD4 exome

AF:

0.00875

AC:

9603

AN:

1097700

Hom.:

862

Cov.:

AF XY:

0.00722

AC XY:

2622

AN XY:

363092

show subpopulations

African (AFR)

AF:

0.287

AC:

7571

AN:

26377

American (AMR)

AF:

0.0157

AC:

551

AN:

35166

Ashkenazi Jewish (ASJ)

AF:

0.00175

AC:

AN:

19379

East Asian (EAS)

AF:

0.00

AC:

AN:

30189

South Asian (SAS)

AF:

0.00111

AC:

AN:

54032

European-Finnish (FIN)

AF:

0.0000247

AC:

AN:

40488

Middle Eastern (MID)

AF:

0.0193

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.000349

AC:

294

AN:

841866

Other (OTH)

AF:

0.0220

AC:

1012

AN:

46067

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

349

698

1048

1397

1746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

226

452

678

904

1130

<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:

0.0815

AC:

9077

AN:

111334

Hom.:

923

Cov.:

AF XY:

0.0729

AC XY:

2445

AN XY:

33562

show subpopulations

African (AFR)

AF:

0.282

AC:

8561

AN:

30362

American (AMR)

AF:

0.0333

AC:

351

AN:

10555

Ashkenazi Jewish (ASJ)

AF:

0.00302

AC:

AN:

2646

East Asian (EAS)

AF:

0.00

AC:

AN:

3554

South Asian (SAS)

AF:

0.000748

AC:

AN:

2675

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6051

Middle Eastern (MID)

AF:

0.0233

AC:

AN:

215

European-Non Finnish (NFE)

AF:

0.000980

AC:

AN:

53079

Other (OTH)

AF:

0.0648

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

237

474

712

949

1186

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<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:

0.0275

Hom.:

1096

Bravo

AF:

0.0940

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Infantile-onset X-linked spinal muscular atrophy

Benign:2

Jan 12, 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. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 04, 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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0020

(source)

DANN

Benign

0.75

PhyloP100

-3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over