rs149947901

Variant names:

• chrX-47199477-C-A
• rs149947901
• NM_003334.4:c.346-3C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-47199477-C-A
• chrX-47199477-C-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 1P and 12B. PP3 BP6_Very_Strong BS2

The NM_003334.4(UBA1):​c.346-3C>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000511 in 1,210,196 control chromosomes in the GnomAD database, including 2 homozygotes. There are 168 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0025 (2 hom., 73 hem., cov: 23)
  • Exomes 𝑓: 0.00031 (0 hom. 95 hem.)
• Consequence: UBA1 NM_003334.4 splice_region, intron
• Scores: Splicing: ADA: 0.9916
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.278
• 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, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• inflammatory disease

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
• BP6: Variant X-47199477-C-A is Benign according to our data. Variant chrX-47199477-C-A is described in ClinVar as Benign. ClinVar VariationId is 533622.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 2 XL,Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA1	NM_003334.4	c.346-3C>A		splice_region_variant, intron_variant	Intron 4 of 25	ENST00000335972.11	NP_003325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA1	ENST00000335972.11	c.346-3C>A		splice_region_variant, intron_variant	Intron 4 of 25	1	NM_003334.4	ENSP00000338413.6

Frequencies

GnomAD3 genomes AF: 0.00245 AC: 274 AN: 111888 Hom.: 2 Cov.: 23

Gnomad AFR AF: 0.00850

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000944

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: 0.00

Gnomad OTH AF: 0.00200

GnomAD2 exomes AF: 0.000752 AC: 138 AN: 183493 AF XY: 0.000456

Gnomad AFR exome AF: 0.00942

Gnomad AMR exome AF: 0.000328

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000122

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000312 AC: 343 AN: 1098255 Hom.: 0 Cov.: 33 AF XY: 0.000261 AC XY: 95 AN XY: 363609

African (AFR) AF: 0.0112 AC: 297 AN: 26403

American (AMR) AF: 0.000341 AC: 12 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19386

East Asian (EAS) AF: 0.00 AC: 0 AN: 30206

South Asian (SAS) AF: 0.000129 AC: 7 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40527

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842142

Other (OTH) AF: 0.000542 AC: 25 AN: 46098

GnomAD4 genome AF: 0.00247 AC: 276 AN: 111941 Hom.: 2 Cov.: 23 AF XY: 0.00214 AC XY: 73 AN XY: 34109

African (AFR) AF: 0.00855 AC: 263 AN: 30775

American (AMR) AF: 0.000943 AC: 10 AN: 10610

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2656

East Asian (EAS) AF: 0.00 AC: 0 AN: 3564

South Asian (SAS) AF: 0.00 AC: 0 AN: 2684

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6113

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 217

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53118

Other (OTH) AF: 0.00197 AC: 3 AN: 1520

Alfa AF: 0.00250 Hom.: 8

Bravo AF: 0.00340

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Infantile-onset X-linked spinal muscular atrophy Benign:1

Jan 10, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.3
DANN	Benign	0.88
PhyloP100		0.28
Mutation Taster		=83/17	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.81
SpliceAI score (max)		0.070		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: rs149947901; hg19: chrX-47058876;