11-124637068-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_170601.5(SIAE):c.1455G>A(p.Trp485*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_170601.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SIAE | NM_170601.5 | c.1455G>A | p.Trp485* | stop_gained | Exon 10 of 10 | ENST00000263593.8 | NP_733746.1 | |
SIAE | NM_001199922.2 | c.1350G>A | p.Trp450* | stop_gained | Exon 12 of 12 | NP_001186851.1 | ||
SIAE | XM_047427132.1 | c.882G>A | p.Trp294* | stop_gained | Exon 7 of 7 | XP_047283088.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SIAE | ENST00000263593.8 | c.1455G>A | p.Trp485* | stop_gained | Exon 10 of 10 | 1 | NM_170601.5 | ENSP00000263593.3 | ||
SIAE | ENST00000618733.4 | c.1350G>A | p.Trp450* | stop_gained | Exon 12 of 12 | 1 | ENSP00000478211.1 | |||
SIAE | ENST00000545756.5 | c.1350G>A | p.Trp450* | stop_gained | Exon 11 of 11 | 5 | ENSP00000437877.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251456Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135900
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461894Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with SIAE-related conditions. This variant is present in population databases (rs769411422, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Trp485*) in the SIAE gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 39 amino acid(s) of the SIAE protein. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at