chr1-74489226-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4BS1_SupportingBS2_Supporting
The NM_015978.3(TNNI3K):c.2159A>G(p.Glu720Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,612,302 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. E720D) has been classified as Uncertain significance.
Frequency
Consequence
NM_015978.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNI3K | NM_015978.3 | c.2159A>G | p.Glu720Gly | missense_variant | 22/25 | ENST00000326637.8 | |
FPGT-TNNI3K | NM_001112808.3 | c.2462A>G | p.Glu821Gly | missense_variant | 24/27 | ||
LRRC53 | NM_001382280.1 | c.-26-5851T>C | intron_variant | ENST00000294635.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNI3K | ENST00000326637.8 | c.2159A>G | p.Glu720Gly | missense_variant | 22/25 | 1 | NM_015978.3 | P1 | |
LRRC53 | ENST00000294635.5 | c.-26-5851T>C | intron_variant | 5 | NM_001382280.1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000561 AC: 14AN: 249574Hom.: 0 AF XY: 0.0000593 AC XY: 8AN XY: 134944
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1459988Hom.: 0 Cov.: 30 AF XY: 0.0000124 AC XY: 9AN XY: 726250
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152314Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 10, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 720 of the TNNI3K protein (p.Glu720Gly). This variant is present in population databases (rs537212164, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with TNNI3K-related conditions. ClinVar contains an entry for this variant (Variation ID: 1483704). 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 tolerated. 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