Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_003334.4(UBA1):c.2364C>T(p.Ala788Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000976 in 1,210,213 control chromosomes in the GnomAD database, including 11 homozygotes. There are 345 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 0.0050 ( 2 hom., 163 hem., cov: 22)

Exomes 𝑓: 0.00056 ( 9 hom. 182 hem. )

Consequence

UBA1
NM_003334.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.717

Publications

0 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant X-47211125-C-T is Benign according to our data. Variant chrX-47211125-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 368344.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.717 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00504 (565/112188) while in subpopulation AFR AF = 0.0175 (539/30881). AF 95% confidence interval is 0.0162. There are 2 homozygotes in GnomAd4. There are 163 alleles in the male GnomAd4 subpopulation. Median coverage is 22. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 XL,Unknown gene

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.2364C>T	p.Ala788Ala	synonymous	Exon 20 of 26	NP_003325.2
UBA1	NM_001440807.1		c.2406C>T	p.Ala802Ala	synonymous	Exon 21 of 27	NP_001427736.1
UBA1	NM_001440809.1		c.2382C>T	p.Ala794Ala	synonymous	Exon 21 of 27	NP_001427738.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
UBA1	ENST00000335972.11	TSL:1 MANE Select	c.2364C>T	p.Ala788Ala	synonymous	Exon 20 of 26	ENSP00000338413.6
UBA1	ENST00000377351.8	TSL:1	c.2364C>T	p.Ala788Ala	synonymous	Exon 20 of 26	ENSP00000366568.4
UBA1	ENST00000377269.3	TSL:2	c.708C>T	p.Ala236Ala	synonymous	Exon 4 of 10	ENSP00000366481.3

Frequencies

GnomAD3 genomes

AF:

0.00504

AC:

565

AN:

112137

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00160

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:

0.0000564

Gnomad OTH

AF:

0.00401

GnomAD2 exomes

AF:

0.00148

AC:

271

AN:

183053

AF XY:

0.000963

show subpopulations

Gnomad AFR exome

AF:

0.0187

Gnomad AMR exome

AF:

0.000839

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.000221

GnomAD4 exome

AF:

0.000561

AC:

616

AN:

1098025

Hom.:

Cov.:

AF XY:

0.000501

AC XY:

182

AN XY:

363403

show subpopulations

African (AFR)

AF:

0.0198

AC:

523

AN:

26403

American (AMR)

AF:

0.00111

AC:

AN:

35207

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19385

East Asian (EAS)

AF:

0.00

AC:

AN:

30206

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40339

Middle Eastern (MID)

AF:

0.000242

AC:

AN:

4137

European-Non Finnish (NFE)

AF:

0.00000950

AC:

AN:

842108

Other (OTH)

AF:

0.000955

AC:

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00504

AC:

565

AN:

112188

Hom.:

Cov.:

AF XY:

0.00474

AC XY:

163

AN XY:

34356

show subpopulations

African (AFR)

AF:

0.0175

AC:

539

AN:

30881

American (AMR)

AF:

0.00160

AC:

AN:

10657

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3560

South Asian (SAS)

AF:

0.00

AC:

AN:

2698

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6140

Middle Eastern (MID)

AF:

0.00

AC:

AN:

213

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53192

Other (OTH)

AF:

0.00396

AC:

AN:

1515

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

117

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:

0.00299

Hom.:

Bravo

AF:

0.00586

ClinVar

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

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

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

6.9

(source)

DANN

Benign

0.66

PhyloP100

-0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

NM_003334.4:c.2364C>T

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over