rs1556793265
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_003334.4(UBA1):c.2371C>T(p.Leu791=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,098,037 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0000018 ( 0 hom. 2 hem. )
Consequence
UBA1
NM_003334.4 synonymous
NM_003334.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.50
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
?
Variant X-47211132-C-T is Benign according to our data. Variant chrX-47211132-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 465033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.5 with no splicing effect.
BS2
?
High Hemizygotes in GnomAdExome4 at 2 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBA1 | NM_003334.4 | c.2371C>T | p.Leu791= | synonymous_variant | 20/26 | ENST00000335972.11 | |
LOC105373194 | XR_949047.4 | n.278-5782G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBA1 | ENST00000335972.11 | c.2371C>T | p.Leu791= | synonymous_variant | 20/26 | 1 | NM_003334.4 | P1 | |
UBA1 | ENST00000377351.8 | c.2371C>T | p.Leu791= | synonymous_variant | 20/26 | 1 | P1 | ||
UBA1 | ENST00000377269.3 | c.715C>T | p.Leu239= | synonymous_variant | 4/10 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183049Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67517
GnomAD3 exomes
AF:
AC:
1
AN:
183049
Hom.:
AF XY:
AC XY:
0
AN XY:
67517
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000182 AC: 2AN: 1098037Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 2AN XY: 363419
GnomAD4 exome
AF:
AC:
2
AN:
1098037
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
363419
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Infantile-onset X-linked spinal muscular atrophy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at