1-74471075-C-CTCAG
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_001382280.1(LRRC53):c.2546_2547insCTGA(p.Glu849AspfsTer2) variant causes a stop gained, frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00002 in 400,746 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )
Consequence
LRRC53
NM_001382280.1 stop_gained, frameshift
NM_001382280.1 stop_gained, frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.499
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 Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
?
Stoplost variant in NM_001382280.1 Downstream stopcodon found after 3 codons.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
|---|---|---|---|---|---|---|---|
| LRRC53 | NM_001382280.1 | c.2546_2547insCTGA | p.Glu849AspfsTer2 | stop_gained, frameshift_variant | 5/5 | ENST00000294635.5 | |
| TNNI3K | NM_015978.3 | c.2121+7526_2121+7529dup | intron_variant | ENST00000326637.8 | |||
| FPGT-TNNI3K | NM_001112808.3 | c.2424+7526_2424+7529dup | intron_variant |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| LRRC53 | ENST00000294635.5 | c.2546_2547insCTGA | p.Glu849AspfsTer2 | stop_gained, frameshift_variant | 5/5 | 5 | NM_001382280.1 | P1 | |
| TNNI3K | ENST00000326637.8 | c.2121+7526_2121+7529dup | intron_variant | 1 | NM_015978.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000161 AC: 4AN: 248440Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 125874
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152306Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74472
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Atrial conduction disease Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jun 10, 2021 | - - |
Computational scores
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Name
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Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at