rs2230147

Variant names:

• chrX-47210862-G-A
• rs2230147
• NM_003334.4:c.2220G>A
• UBA1 p.Pro740Pro

Your query was ambiguous. Multiple possible variants found:

• chrX-47210862-G-A
• chrX-47210862-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -3.28
• Publications: 3 publications found

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: Genomics England PanelApp, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• inflammatory disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

LOC105373194 (HGNC:):

ACMG classification

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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA1	NM_003334.4	MANE Select	c.2220G>A	p.Pro740Pro	synonymous	Exon 19 of 26	NP_003325.2
	UBA1	NM_001440807.1		c.2262G>A	p.Pro754Pro	synonymous	Exon 20 of 27	NP_001427736.1
	UBA1	NM_001440809.1		c.2238G>A	p.Pro746Pro	synonymous	Exon 20 of 27	NP_001427738.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA1	ENST00000335972.11	TSL:1 MANE Select	c.2220G>A	p.Pro740Pro	synonymous	Exon 19 of 26	ENSP00000338413.6	P22314-1
	UBA1	ENST00000377351.8	TSL:1	c.2220G>A	p.Pro740Pro	synonymous	Exon 19 of 26	ENSP00000366568.4	P22314-1
	UBA1	ENST00000880189.1		c.2355G>A	p.Pro785Pro	synonymous	Exon 20 of 27	ENSP00000550248.1

Frequencies

GnomAD3 genomes AF: 0.0812 AC: 9036 AN: 111280 Hom.: 917 Cov.: 22

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

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.: 32 AF XY: 0.00722 AC XY: 2622 AN XY: 363092

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: 34 AN: 19379

East Asian (EAS) AF: 0.00 AC: 0 AN: 30189

South Asian (SAS) AF: 0.00111 AC: 60 AN: 54032

European-Finnish (FIN) AF: 0.0000247 AC: 1 AN: 40488

Middle Eastern (MID) AF: 0.0193 AC: 80 AN: 4136

European-Non Finnish (NFE) AF: 0.000349 AC: 294 AN: 841866

Other (OTH) AF: 0.0220 AC: 1012 AN: 46067

GnomAD4 genome AF: 0.0815 AC: 9077 AN: 111334 Hom.: 923 Cov.: 22 AF XY: 0.0729 AC XY: 2445 AN XY: 33562

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: 8 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3554

South Asian (SAS) AF: 0.000748 AC: 2 AN: 2675

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6051

Middle Eastern (MID) AF: 0.0233 AC: 5 AN: 215

European-Non Finnish (NFE) AF: 0.000980 AC: 52 AN: 53079

Other (OTH) AF: 0.0648 AC: 98 AN: 1512

Alfa AF: 0.0275 Hom.: 1096

Bravo AF: 0.0940

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Infantile-onset X-linked spinal muscular atrophy (2)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0020
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)

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

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

Other links and lift over

dbSNP: rs2230147;

hg19: chrX-47070261;

COSMIC: COSV107430043;

COSMIC: COSV107430043;