rs139492208

Variant names:

• chrX-47212812-A-G
• rs139492208
• NM_003334.4:c.2595A>G

Your query was ambiguous. Multiple possible variants found:

• chrX-47212812-A-G
• chrX-47212812-A-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_003334.4(UBA1):​c.2595A>G​(p.Ala865Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000422 in 1,209,932 control chromosomes in the GnomAD database, including 4 homozygotes. There are 131 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A865A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., 71 hem., cov: 22)
  • Exomes 𝑓: 0.00023 (2 hom. 60 hem.)
• Consequence: UBA1 NM_003334.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.505
• Publications: 0 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: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet
• inflammatory disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

LOC105373194 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant X-47212812-A-G is Benign according to our data. Variant chrX-47212812-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 465034.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.505 with no splicing effect.
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA1	NM_003334.4	MANE Select	c.2595A>G	p.Ala865Ala	synonymous	Exon 22 of 26	NP_003325.2
	UBA1	NM_001440807.1		c.2637A>G	p.Ala879Ala	synonymous	Exon 23 of 27	NP_001427736.1
	UBA1	NM_001440809.1		c.2613A>G	p.Ala871Ala	synonymous	Exon 23 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.2595A>G	p.Ala865Ala	synonymous	Exon 22 of 26	ENSP00000338413.6	P22314-1
	UBA1	ENST00000377351.8	TSL:1	c.2595A>G	p.Ala865Ala	synonymous	Exon 22 of 26	ENSP00000366568.4	P22314-1
	UBA1	ENST00000880189.1		c.2730A>G	p.Ala910Ala	synonymous	Exon 23 of 27	ENSP00000550248.1

Frequencies

GnomAD3 genomes AF: 0.00234 AC: 262 AN: 111746 Hom.: 2 Cov.: 22

Gnomad AFR AF: 0.00825

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000474

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: 0.0000188

Gnomad OTH AF: 0.00199

GnomAD2 exomes AF: 0.000744 AC: 136 AN: 182805 AF XY: 0.000476

Gnomad AFR exome AF: 0.0101

Gnomad AMR exome AF: 0.000110

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 AF: 0.000227 AC: 249 AN: 1098132 Hom.: 2 Cov.: 31 AF XY: 0.000165 AC XY: 60 AN XY: 363490

African (AFR) AF: 0.00807 AC: 213 AN: 26402

American (AMR) AF: 0.000227 AC: 8 AN: 35205

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19383

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.0000554 AC: 3 AN: 54113

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000594 AC: 5 AN: 842081

Other (OTH) AF: 0.000434 AC: 20 AN: 46094

GnomAD4 genome AF: 0.00233 AC: 261 AN: 111800 Hom.: 2 Cov.: 22 AF XY: 0.00209 AC XY: 71 AN XY: 33986

African (AFR) AF: 0.00820 AC: 252 AN: 30745

American (AMR) AF: 0.000473 AC: 5 AN: 10568

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3576

South Asian (SAS) AF: 0.00 AC: 0 AN: 2661

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 219

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53140

Other (OTH) AF: 0.00196 AC: 3 AN: 1527

Alfa AF: 0.00130 Hom.: 8

Bravo AF: 0.00229

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)
-	-	1	Infantile-onset X-linked spinal muscular atrophy (1)
-	-	1	not specified (1)
-	-	1	UBA1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	8.7
DANN	Benign	0.60
PhyloP100		-0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs139492208; hg19: chrX-47072211;