chr11-124637100-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_170601.5(SIAE):c.1423G>A(p.Val475Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. V475V) has been classified as Uncertain significance.
Frequency
Consequence
NM_170601.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SIAE | NM_170601.5 | c.1423G>A | p.Val475Met | missense_variant | 10/10 | ENST00000263593.8 | |
SIAE | NM_001199922.2 | c.1318G>A | p.Val440Met | missense_variant | 12/12 | ||
SIAE | XM_047427132.1 | c.850G>A | p.Val284Met | missense_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SIAE | ENST00000263593.8 | c.1423G>A | p.Val475Met | missense_variant | 10/10 | 1 | NM_170601.5 | P2 | |
SIAE | ENST00000618733.4 | c.1318G>A | p.Val440Met | missense_variant | 12/12 | 1 | A2 | ||
SIAE | ENST00000545756.5 | c.1318G>A | p.Val440Met | missense_variant | 11/11 | 5 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251466Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135910
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 05, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1979512). This variant has not been reported in the literature in individuals affected with SIAE-related conditions. This variant is present in population databases (rs765363693, gnomAD 0.005%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 475 of the SIAE protein (p.Val475Met). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at