rs2230147

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003334.4(UBA1):c.2220G>A(p.Pro740=) 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

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 -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. Variant chrX-47210862-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
UBA1	NM_003334.4 linkuse as main transcript	c.2220G>A	p.Pro740=	synonymous_variant	19/26	ENST00000335972.11	NP_003325.2
LOC105373194	XR_949047.4 linkuse as main transcript	n.278-5512C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBA1	ENST00000335972.11 linkuse as main transcript	c.2220G>A	p.Pro740=	synonymous_variant	19/26	1	NM_003334.4	ENSP00000338413	P1	P22314-1
UBA1	ENST00000377351.8 linkuse as main transcript	c.2220G>A	p.Pro740=	synonymous_variant	19/26	1		ENSP00000366568	P1	P22314-1
UBA1	ENST00000377269.3 linkuse as main transcript	c.564G>A	p.Pro188=	synonymous_variant	3/10	2		ENSP00000366481

Frequencies

GnomAD3 genomes

AF:

0.0812

AC:

9036

AN:

111280

Hom.:

917

Cov.:

AF XY:

0.0723

AC XY:

2422

AN XY:

33498

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

GnomAD3 exomes

AF:

0.0229

AC:

4140

AN:

181091

Hom.:

443

AF XY:

0.0144

AC XY:

948

AN XY:

65691

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 SAS exome

AF:

0.000748

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

Gnomad4 AFR exome

AF:

0.287

Gnomad4 AMR exome

AF:

0.0157

Gnomad4 ASJ exome

AF:

0.00175

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.000349

Gnomad4 OTH exome

AF:

0.0220

GnomAD4 genome

AF:

0.0815

AC:

9077

AN:

111334

Hom.:

923

Cov.:

AF XY:

0.0729

AC XY:

2445

AN XY:

33562

show subpopulations

Gnomad4 AFR

AF:

0.282

Gnomad4 AMR

AF:

0.0333

Gnomad4 ASJ

AF:

0.00302

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000748

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000980

Gnomad4 OTH

AF:

0.0648

Alfa

AF:

0.0120

Hom.:

275

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 04, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0020

DANN

Benign

0.75

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

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