X-47198248-A-T

Variant names:

• chrX-47198248-A-T
• rs4468050
• NM_003334.4:c.1-555A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003334.4(UBA1):​c.1-555A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000115 in 869,412 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes 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: 22)
  • Exomes 𝑓: 0.0000012 (0 hom. 1 hem.)
• Consequence: UBA1 NM_003334.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.641

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08523613).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA1	NM_003334.4	c.1-555A>T		intron_variant	Intron 1 of 25	ENST00000335972.11	NP_003325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA1	ENST00000335972.11	c.1-555A>T		intron_variant	Intron 1 of 25	1	NM_003334.4	ENSP00000338413.6

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000115 AC: 1 AN: 869412 Hom.: 0 Cov.: 42 AF XY: 0.00000354 AC XY: 1 AN XY: 282298

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: 0.0000210

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.070
DANN	Benign	0.36
DEOGEN2	Benign	0.011	T;.
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.27	T;T
MetaRNN	Benign	0.085	T;T
MetaSVM	Benign	-0.66	T
PROVEAN	Benign	-0.15	N;N
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D;D
MutPred		0.16		Loss of methylation at K20 (P = 0.1182);Loss of methylation at K20 (P = 0.1182);
MVP		0.26
ClinPred		0.073	T
GERP RS		-3.1

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

LitVar

Other links and lift over

dbSNP: rs4468050; hg19: chrX-47057647;