5-95464674-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_014639.4(SKIC3):c.4628T>A(p.Val1543Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000093 in 1,612,806 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1543A) has been classified as Uncertain significance.
Frequency
Consequence
NM_014639.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SKIC3 | NM_014639.4 | c.4628T>A | p.Val1543Glu | missense_variant | 43/43 | ENST00000358746.7 | |
SKIC3 | XM_047417937.1 | c.4628T>A | p.Val1543Glu | missense_variant | 43/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SKIC3 | ENST00000358746.7 | c.4628T>A | p.Val1543Glu | missense_variant | 43/43 | 1 | NM_014639.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250500Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135398
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1460722Hom.: 0 Cov.: 29 AF XY: 0.0000110 AC XY: 8AN XY: 726678
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74280
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 05, 2021 | This sequence change replaces valine with glutamic acid at codon 1543 of the TTC37 protein (p.Val1543Glu). The valine residue is weakly conserved and there is a moderate physicochemical difference between valine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with TTC37-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at