rs369149321
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_003283.6(TNNT1):c.156G>A(p.Pro52=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,613,964 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 1 hom. )
Consequence
TNNT1
NM_003283.6 synonymous
NM_003283.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.22
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 -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 19-55141893-C-T is Benign according to our data. Variant chr19-55141893-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 387414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.22 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TNNT1 | NM_003283.6 | c.156G>A | p.Pro52= | synonymous_variant | 7/14 | ENST00000588981.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TNNT1 | ENST00000588981.6 | c.156G>A | p.Pro52= | synonymous_variant | 7/14 | 1 | NM_003283.6 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152094Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251396Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135860
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GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461752Hom.: 1 Cov.: 31 AF XY: 0.0000509 AC XY: 37AN XY: 727182
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GnomAD4 genome ? AF: 0.000210 AC: 32AN: 152212Hom.: 0 Cov.: 32 AF XY: 0.000202 AC XY: 15AN XY: 74424
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
TNNT1-related condition Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 23, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 13, 2019 | - - |
Nemaline myopathy 5 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 02, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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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