1-74236087-G-C
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_015978.3(TNNI3K):c.41-15G>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000094 in 1,595,696 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 Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000097 ( 0 hom. )
Consequence
TNNI3K
NM_015978.3 splice_polypyrimidine_tract, intron
NM_015978.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.712
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 1-74236087-G-C is Benign according to our data. Variant chr1-74236087-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1536878.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNI3K | NM_015978.3 | c.41-15G>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000326637.8 | |||
FPGT-TNNI3K | NM_001112808.3 | c.344-15G>C | splice_polypyrimidine_tract_variant, intron_variant | ||||
FPGT-TNNI3K | NM_001199327.2 | c.344-15G>C | splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNI3K | ENST00000326637.8 | c.41-15G>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_015978.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000660 AC: 1AN: 151516Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000204 AC: 5AN: 244750Hom.: 0 AF XY: 0.00000755 AC XY: 1AN XY: 132448
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GnomAD4 exome AF: 0.00000969 AC: 14AN: 1444180Hom.: 0 Cov.: 28 AF XY: 0.0000139 AC XY: 10AN XY: 718598
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GnomAD4 genome AF: 0.00000660 AC: 1AN: 151516Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73992
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at