1-74236090-C-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015978.3(TNNI3K):c.41-12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,445,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )
Consequence
TNNI3K
NM_015978.3 intron
NM_015978.3 intron
Scores
2
Splicing: ADA: 0.0004700
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.31
Publications
0 publications found
Genes affected
TNNI3K (HGNC:19661): (TNNI3 interacting kinase) This gene encodes a protein that belongs to the MAP kinase kinase kinase (MAPKKK) family of protein kinases. The protein contains ankyrin repeat, protein kinase and serine-rich domains and is thought to play a role in cardiac physiology. [provided by RefSeq, Sep 2012]
FPGT-TNNI3K (HGNC:42952): (FPGT-TNNI3K readthrough) Enables protein C-terminus binding activity; protein kinase activity; and troponin I binding activity. Involved in protein phosphorylation and regulation of heart contraction. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.76).
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| TNNI3K | NM_015978.3 | c.41-12C>A | intron_variant | Intron 1 of 24 | ENST00000326637.8 | NP_057062.1 | ||
| FPGT-TNNI3K | NM_001112808.3 | c.344-12C>A | intron_variant | Intron 3 of 26 | NP_001106279.3 | |||
| FPGT-TNNI3K | NM_001199327.2 | c.344-12C>A | intron_variant | Intron 3 of 23 | NP_001186256.3 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.92e-7 AC: 1AN: 1445924Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1AN XY: 719452 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
1
AN:
1445924
Hom.:
Cov.:
29
AF XY:
AC XY:
1
AN XY:
719452
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32634
American (AMR)
AF:
AC:
0
AN:
43212
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25632
East Asian (EAS)
AF:
AC:
0
AN:
39122
South Asian (SAS)
AF:
AC:
1
AN:
84432
European-Finnish (FIN)
AF:
AC:
0
AN:
52890
Middle Eastern (MID)
AF:
AC:
0
AN:
5466
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1102974
Other (OTH)
AF:
AC:
0
AN:
59562
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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