rs201253044

Variant names:

• chrX-47198858-C-G
• rs201253044
• NM_003334.4:c.56C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-47198858-C-G
• chrX-47198858-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003334.4(UBA1):​c.56C>G​(p.Pro19Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,264 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 0 hem.)
• Consequence: UBA1 NM_003334.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.25
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2553755).

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.56C>G	p.Pro19Arg	missense	Exon 2 of 26	NP_003325.2
	UBA1	NM_001440807.1		c.98C>G	p.Pro33Arg	missense	Exon 3 of 27	NP_001427736.1
	UBA1	NM_001440809.1		c.74C>G	p.Pro25Arg	missense	Exon 3 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.56C>G	p.Pro19Arg	missense	Exon 2 of 26	ENSP00000338413.6	P22314-1
	UBA1	ENST00000377351.8	TSL:1	c.56C>G	p.Pro19Arg	missense	Exon 2 of 26	ENSP00000366568.4	P22314-1
	UBA1	ENST00000880189.1		c.56C>G	p.Pro19Arg	missense	Exon 2 of 27	ENSP00000550248.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000182 AC: 2 AN: 1098264 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363618

African (AFR) AF: 0.0000757 AC: 2 AN: 26403

American (AMR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 54149

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 842146

Other (OTH) AF: 0.00 AC: 0 AN: 46098

GnomAD4 genome Cov.: 24

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.85	T
M_CAP	Pathogenic	0.60	D
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	0.34	N
PhyloP100		7.3
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	0.37	N
REVEL	Benign	0.10
Sift	Benign	0.49	T
Sift4G	Benign	0.53	T
Polyphen		0.057	B
Vest4		0.25
MutPred		0.16		Gain of MoRF binding (P = 0.0065)
MVP		0.52
MPC		0.56
ClinPred		0.75	D
GERP RS		5.3
Varity_R		0.17
gMVP		0.73
Mutation Taster		=86/14	polymorphism

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: rs201253044; hg19: chrX-47058257;