1-74235474-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_015978.3(TNNI3K):c.23C>A(p.Pro8Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000294 in 1,359,278 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. P8S) has been classified as Uncertain significance.
Frequency
Consequence
NM_015978.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNI3K | NM_015978.3 | c.23C>A | p.Pro8Gln | missense_variant | 1/25 | ENST00000326637.8 | |
FPGT-TNNI3K | NM_001112808.3 | c.344-628C>A | intron_variant | ||||
FPGT-TNNI3K | NM_001199327.2 | c.344-628C>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNI3K | ENST00000326637.8 | c.23C>A | p.Pro8Gln | missense_variant | 1/25 | 1 | NM_015978.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000442 AC: 1AN: 226484Hom.: 0 AF XY: 0.00000810 AC XY: 1AN XY: 123458
GnomAD4 exome AF: 0.00000294 AC: 4AN: 1359278Hom.: 0 Cov.: 23 AF XY: 0.00000294 AC XY: 2AN XY: 680736
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 03, 2023 | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 8 of the TNNI3K protein (p.Pro8Gln). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TNNI3K-related conditions. 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. 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