chr1-74489195-C-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PP3_ModerateBP6BS1BS2
The NM_015978.3(TNNI3K):c.2128C>A(p.Pro710Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000199 in 1,610,530 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 Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P710P) has been classified as Likely benign.
Frequency
Consequence
NM_015978.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNI3K | NM_015978.3 | c.2128C>A | p.Pro710Thr | missense_variant | 22/25 | ENST00000326637.8 | |
FPGT-TNNI3K | NM_001112808.3 | c.2431C>A | p.Pro811Thr | missense_variant | 24/27 | ||
LRRC53 | NM_001382280.1 | c.-26-5820G>T | intron_variant | ENST00000294635.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNI3K | ENST00000326637.8 | c.2128C>A | p.Pro710Thr | missense_variant | 22/25 | 1 | NM_015978.3 | P1 | |
LRRC53 | ENST00000294635.5 | c.-26-5820G>T | intron_variant | 5 | NM_001382280.1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152140Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000564 AC: 14AN: 248426Hom.: 0 AF XY: 0.0000447 AC XY: 6AN XY: 134368
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1458390Hom.: 0 Cov.: 30 AF XY: 0.0000165 AC XY: 12AN XY: 725502
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74310
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 22, 2023 | The c.2128C>A (p.P710T) alteration is located in exon 22 (coding exon 22) of the TNNI3K gene. This alteration results from a C to A substitution at nucleotide position 2128, causing the proline (P) at amino acid position 710 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at