X-47198894-C-T

Variant names:

• chrX-47198894-C-T
• NM_003334.4:c.92C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003334.4(UBA1):​c.92C>T​(p.Ser31Phe) variant causes a missense change. The variant allele was found at a frequency of 0.000000911 in 1,098,238 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.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: UBA1 NM_003334.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.41

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27352333).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA1	NM_003334.4	c.92C>T	p.Ser31Phe	missense_variant	Exon 2 of 26	ENST00000335972.11	NP_003325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA1	ENST00000335972.11	c.92C>T	p.Ser31Phe	missense_variant	Exon 2 of 26	1	NM_003334.4	ENSP00000338413.6

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1098238 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363592

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000119

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T;.;T;T;T;T;.
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.73	T;T;T;T;T;.;T
M_CAP	Pathogenic	0.54	D
MetaRNN	Benign	0.27	T;T;T;T;T;T;T
MetaSVM	Benign	-0.47	T
MutationAssessor	Benign	0.97	L;.;.;.;.;L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.86	N;N;N;N;N;N;N
REVEL	Benign	0.042
Sift	Benign	0.26	T;T;T;T;T;T;T
Sift4G	Benign	0.071	T;T;D;T;D;T;D
Polyphen		0.0	B;.;.;.;.;B;.
Vest4		0.22
MutPred		0.25		Loss of phosphorylation at S31 (P = 0.035);Loss of phosphorylation at S31 (P = 0.035);.;.;.;Loss of phosphorylation at S31 (P = 0.035);.;
MVP		0.55
MPC		0.50
ClinPred		0.69	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.19
gMVP		0.80

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-47058293;