rs147398292

Variant names:

• chrX-47198545-A-G
• rs147398292
• NM_003334.4:c.1-258A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003334.4(UBA1):​c.1-258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 111,291 control chromosomes in the GnomAD database, including 51 homozygotes. There are 597 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.020 (51 hom., 597 hem., cov: 23)
• Consequence: UBA1 NM_003334.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0850
• 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: Orphanet, Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• inflammatory disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant X-47198545-A-G is Benign according to our data. Variant chrX-47198545-A-G is described in ClinVar as Benign. ClinVar VariationId is 1296620.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0678 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.1-258A>G		intron	N/A	NP_003325.2
	UBA1	NM_001440807.1		c.42+190A>G		intron	N/A	NP_001427736.1
	UBA1	NM_001440809.1		c.19-258A>G		intron	N/A	NP_001427738.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBA1	ENST00000335972.11	TSL:1 MANE Select	c.1-258A>G		intron	N/A	ENSP00000338413.6	P22314-1
	UBA1	ENST00000377351.8	TSL:1	c.1-258A>G		intron	N/A	ENSP00000366568.4	P22314-1
	UBA1	ENST00000880172.1		c.-84A>G		5_prime_UTR	Exon 2 of 27	ENSP00000550231.1

Frequencies

GnomAD3 genomes AF: 0.0201 AC: 2237 AN: 111238 Hom.: 50 Cov.: 23

Gnomad AFR AF: 0.0702

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00592

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000754

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00833

Gnomad NFE AF: 0.000283

Gnomad OTH AF: 0.0120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0202 AC: 2243 AN: 111291 Hom.: 51 Cov.: 23 AF XY: 0.0178 AC XY: 597 AN XY: 33517

African (AFR) AF: 0.0702 AC: 2144 AN: 30527

American (AMR) AF: 0.00591 AC: 62 AN: 10489

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

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

South Asian (SAS) AF: 0.000757 AC: 2 AN: 2643

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5994

Middle Eastern (MID) AF: 0.00913 AC: 2 AN: 219

European-Non Finnish (NFE) AF: 0.000283 AC: 15 AN: 53029

Other (OTH) AF: 0.0119 AC: 18 AN: 1517

Alfa AF: 0.0103 Hom.: 49

Bravo AF: 0.0233

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.4
DANN	Benign	0.63
PhyloP100		0.085
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs147398292; hg19: chrX-47057944;