1-74489172-C-CT
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1
The NM_015978.3(TNNI3K):c.2122-11dup 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 0.0258 in 1,601,692 control chromosomes in the GnomAD database, including 2,690 homozygotes. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.083 ( 1363 hom., cov: 31)
Exomes 𝑓: 0.020 ( 1327 hom. )
Consequence
TNNI3K
NM_015978.3 splice_polypyrimidine_tract, intron
NM_015978.3 splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.01
Genes affected
LRRC53 (HGNC:25255): (leucine rich repeat containing 53) Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
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.
BP6
Variant 1-74489172-C-CT is Benign according to our data. Variant chr1-74489172-C-CT is described in ClinVar as [Benign]. Clinvar id is 1603128.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LRRC53 | NM_001382280.1 | c.-26-5798_-26-5797insA | intron_variant | ENST00000294635.5 | NP_001369209.1 | |||
TNNI3K | NM_015978.3 | c.2122-11dup | splice_polypyrimidine_tract_variant, intron_variant | ENST00000326637.8 | NP_057062.1 | |||
FPGT-TNNI3K | NM_001112808.3 | c.2425-11dup | splice_polypyrimidine_tract_variant, intron_variant | NP_001106279.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LRRC53 | ENST00000294635.5 | c.-26-5798_-26-5797insA | intron_variant | 5 | NM_001382280.1 | ENSP00000294635 | P1 | |||
TNNI3K | ENST00000326637.8 | c.2122-11dup | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_015978.3 | ENSP00000322251 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0827 AC: 12575AN: 152018Hom.: 1362 Cov.: 31
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GnomAD3 exomes AF: 0.0287 AC: 6908AN: 240924Hom.: 541 AF XY: 0.0241 AC XY: 3140AN XY: 130390
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GnomAD4 exome AF: 0.0198 AC: 28694AN: 1449556Hom.: 1327 Cov.: 30 AF XY: 0.0189 AC XY: 13629AN XY: 720844
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GnomAD4 genome AF: 0.0827 AC: 12580AN: 152136Hom.: 1363 Cov.: 31 AF XY: 0.0804 AC XY: 5978AN XY: 74384
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Computational scores
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at