X-47206074-C-T

Variant names:

• chrX-47206074-C-T
• rs150574055
• NM_003334.4:c.1702C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003334.4(UBA1):​c.1702C>T​(p.Leu568Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000916 in 1,091,843 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: 24)
  • Exomes 𝑓: 9.2e-7 (0 hom. 0 hem.)
• Consequence: UBA1 NM_003334.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 8 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]

LOC105373194 (HGNC:):

INE1 (HGNC:6060): (inactivation escape 1) X chromosome inactivation provides dosage compensation for the expression level of X-linked genes from the single X in males and the two in females. This X chromosome gene is intronless and was identified because its transcription escapes X inactivation in females. This gene does not make a protein.[provided by RefSeq, May 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP7: Synonymous conserved (PhyloP=2.09 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBA1	NM_003334.4	c.1702C>T	p.Leu568Leu	synonymous_variant	Exon 15 of 26	ENST00000335972.11	NP_003325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBA1	ENST00000335972.11	c.1702C>T	p.Leu568Leu	synonymous_variant	Exon 15 of 26	1	NM_003334.4	ENSP00000338413.6
UBA1	ENST00000377351.8	c.1702C>T	p.Leu568Leu	synonymous_variant	Exon 15 of 26	1		ENSP00000366568.4
UBA1	ENST00000490869.1	n.465-4C>T		splice_region_variant, intron_variant	Intron 4 of 5	2
INE1	ENST00000456273.1	n.*209C>T		downstream_gene_variant		6

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 9.16e-7 AC: 1 AN: 1091843 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 358237

African (AFR) AF: 0.00 AC: 0 AN: 26282

American (AMR) AF: 0.00 AC: 0 AN: 34541

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19305

East Asian (EAS) AF: 0.00 AC: 0 AN: 29925

South Asian (SAS) AF: 0.00 AC: 0 AN: 52909

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40087

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4134

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 838824

Other (OTH) AF: 0.00 AC: 0 AN: 45836

GnomAD4 genome Cov.: 24

Alfa AF: 0.00 Hom.: 80

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	3.6
DANN	Benign	0.90
PhyloP100		2.1

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

Other links and lift over

dbSNP: rs150574055; hg19: chrX-47065473;