chr1-74235470-A-G
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_015978.3(TNNI3K):āc.19A>Gā(p.Arg7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000734 in 1,363,142 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 (ā ). Synonymous variant affecting the same amino acid position (i.e. R7R) has been classified as Likely benign.
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.19A>G | p.Arg7Gly | missense_variant | 1/25 | ENST00000326637.8 | |
FPGT-TNNI3K | NM_001112808.3 | c.344-632A>G | intron_variant | ||||
FPGT-TNNI3K | NM_001199327.2 | c.344-632A>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNI3K | ENST00000326637.8 | c.19A>G | p.Arg7Gly | missense_variant | 1/25 | 1 | NM_015978.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000734 AC: 10AN: 1363142Hom.: 0 Cov.: 23 AF XY: 0.00000586 AC XY: 4AN XY: 682400
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Atrial conduction disease Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Molecular Genetics, Royal Melbourne Hospital | Jan 05, 2024 | This sequence change in TNNI3K is predicted to replace arginine with glycine at codon 7, p.(Arg7Gly). The arginine residue is highly conserved (100 vertebrates, UCSC), and is located in the L-fucokinase domain. There is a large physicochemical difference between arginine and glycine. The highest population minor allele frequency in the population database gnomAD v4.0 is 0.0004% (9/1,038,132 alleles) in the European non-Finnish population. To our knowledge, this variant has not been previously reported in the relevant scientific literature or databases. Computational evidence is uninformative for the missense substitution (REVEL = 0.575). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.6.1, this variant is classified as a VARIANT OF UNCERTAIN SIGNIFICANCE. Following criteria are met: PM2_Supporting - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.