rs181679318
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_003282.4(TNNI2):āc.54G>Cā(p.Leu18Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0004 in 1,610,904 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00037 ( 2 hom., cov: 33)
Exomes š: 0.00040 ( 1 hom. )
Consequence
TNNI2
NM_003282.4 synonymous
NM_003282.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.54
Genes affected
TNNI2 (HGNC:11946): (troponin I2, fast skeletal type) This gene encodes a fast-twitch skeletal muscle protein, a member of the troponin I gene family, and a component of the troponin complex including troponin T, troponin C and troponin I subunits. The troponin complex, along with tropomyosin, is responsible for the calcium-dependent regulation of striated muscle contraction. Mouse studies show that this component is also present in vascular smooth muscle and may play a role in regulation of smooth muscle function. In addition to muscle tissues, this protein is found in corneal epithelium, cartilage where it is an inhibitor of angiogenesis to inhibit tumor growth and metastasis, and mammary gland where it functions as a co-activator of estrogen receptor-related receptor alpha. This protein also suppresses tumor growth in human ovarian carcinoma. Mutations in this gene cause myopathy and distal arthrogryposis type 2B. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Mar 2009]
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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=-0.57).
BP6
Variant 11-1840441-G-C is Benign according to our data. Variant chr11-1840441-G-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 287318.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=2, Benign=1}.
BP7
Synonymous conserved (PhyloP=2.54 with no splicing effect.
BS2
High AC in GnomAd4 at 56 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TNNI2 | NM_003282.4 | c.54G>C | p.Leu18Leu | synonymous_variant | 4/8 | ENST00000381911.6 | NP_003273.1 | |
TNNI2 | NM_001145829.2 | c.54G>C | p.Leu18Leu | synonymous_variant | 4/8 | NP_001139301.1 | ||
TNNI2 | NM_001145841.2 | c.54G>C | p.Leu18Leu | synonymous_variant | 2/6 | NP_001139313.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TNNI2 | ENST00000381911.6 | c.54G>C | p.Leu18Leu | synonymous_variant | 4/8 | 2 | NM_003282.4 | ENSP00000371336.1 |
Frequencies
GnomAD3 genomes AF: 0.000368 AC: 56AN: 152262Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000580 AC: 138AN: 238012Hom.: 1 AF XY: 0.000619 AC XY: 81AN XY: 130936
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GnomAD4 exome AF: 0.000404 AC: 589AN: 1458524Hom.: 1 Cov.: 35 AF XY: 0.000398 AC XY: 289AN XY: 725550
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GnomAD4 genome AF: 0.000368 AC: 56AN: 152380Hom.: 2 Cov.: 33 AF XY: 0.000228 AC XY: 17AN XY: 74508
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Sep 13, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 28, 2016 | - - |
Arthrogryposis multiplex congenita Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Arthrogryposis multiplex congenita distal Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2019 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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