chr19-55141216-T-C
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2
The NM_003283.6(TNNT1):āc.279A>Gā(p.Glu93=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000487 in 1,614,226 control chromosomes in the GnomAD database, including 6 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 0.0027 ( 5 hom., cov: 32)
Exomes š: 0.00025 ( 1 hom. )
Consequence
TNNT1
NM_003283.6 synonymous
NM_003283.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.911
Genes affected
TNNT1 (HGNC:11948): (troponin T1, slow skeletal type) This gene encodes a protein that is a subunit of troponin, which is a regulatory complex located on the thin filament of the sarcomere. This complex regulates striated muscle contraction in response to fluctuations in intracellular calcium concentration. This complex is composed of three subunits: troponin C, which binds calcium, troponin T, which binds tropomyosin, and troponin I, which is an inhibitory subunit. This protein is the slow skeletal troponin T subunit. Mutations in this gene cause nemaline myopathy type 5, also known as Amish nemaline myopathy, a neuromuscular disorder characterized by muscle weakness and rod-shaped, or nemaline, inclusions in skeletal muscle fibers which affects infants, resulting in death due to respiratory insufficiency, usually in the second year. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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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=-0.7).
BP6
Variant 19-55141216-T-C is Benign according to our data. Variant chr19-55141216-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 31856.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Likely_benign=1, Uncertain_significance=1, not_provided=1}.
BP7
Synonymous conserved (PhyloP=-0.911 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 5 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNT1 | NM_003283.6 | c.279A>G | p.Glu93= | synonymous_variant | 8/14 | ENST00000588981.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNT1 | ENST00000588981.6 | c.279A>G | p.Glu93= | synonymous_variant | 8/14 | 1 | NM_003283.6 |
Frequencies
GnomAD3 genomes AF: 0.00273 AC: 416AN: 152240Hom.: 5 Cov.: 32
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GnomAD3 exomes AF: 0.000704 AC: 177AN: 251430Hom.: 2 AF XY: 0.000471 AC XY: 64AN XY: 135912
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GnomAD4 exome AF: 0.000252 AC: 368AN: 1461868Hom.: 1 Cov.: 31 AF XY: 0.000206 AC XY: 150AN XY: 727234
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GnomAD4 genome AF: 0.00274 AC: 418AN: 152358Hom.: 5 Cov.: 32 AF XY: 0.00231 AC XY: 172AN XY: 74508
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2Other:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Nemaline myopathy 5 Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 28, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Benign:1Other:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 02, 2021 | - - |
not provided, no classification provided | curation | Leiden Muscular Dystrophy (TNNT1) | Mar 18, 2012 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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