rs1556788657

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003334.4(UBA1):c.1048C>T(p.Arg350Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R350H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 24)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

UBA1
NM_003334.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.59

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, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
inflammatory disease
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

UBA1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23121536).

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.1048C>T	p.Arg350Cys	missense	Exon 10 of 26	NP_003325.2
UBA1	NM_001440807.1		c.1090C>T	p.Arg364Cys	missense	Exon 11 of 27	NP_001427736.1
UBA1	NM_001440809.1		c.1066C>T	p.Arg356Cys	missense	Exon 11 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.1048C>T	p.Arg350Cys	missense	Exon 10 of 26	ENSP00000338413.6	P22314-1
UBA1	ENST00000377351.8	TSL:1	c.1048C>T	p.Arg350Cys	missense	Exon 10 of 26	ENSP00000366568.4	P22314-1
UBA1	ENST00000880189.1		c.1183C>T	p.Arg395Cys	missense	Exon 11 of 27	ENSP00000550248.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

157340

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.20e-7

AC:

AN:

1087260

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

355206

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26133

American (AMR)

AF:

0.00

AC:

AN:

33736

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19216

East Asian (EAS)

AF:

0.00

AC:

AN:

29471

South Asian (SAS)

AF:

0.00

AC:

AN:

52674

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39519

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4122

European-Non Finnish (NFE)

AF:

0.00000120

AC:

AN:

836772

Other (OTH)

AF:

0.00

AC:

AN:

45617

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Infantile-onset X-linked spinal muscular atrophy (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

M_CAP

Benign

0.033

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

1.6

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.9

REVEL

Benign

0.068

Sift

Benign

0.18

Sift4G

Benign

0.18

Polyphen

0.97

Vest4

0.32

MutPred

0.33

Gain of catalytic residue at P349 (P = 0.0104)

MVP

0.20

MPC

0.92

ClinPred

0.93

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.45

gMVP

0.62

Mutation Taster

=83/17

polymorphism

(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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over