15-63042789-C-T
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001018005.2(TPM1):c.-41C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,568,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 7.1e-7 ( 0 hom. )
Consequence
TPM1
NM_001018005.2 5_prime_UTR
NM_001018005.2 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.929
Genes affected
TPM1 (HGNC:12010): (tropomyosin 1) This gene is a member of the tropomyosin family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells. Tropomyosin is composed of two alpha-helical chains arranged as a coiled-coil. It is polymerized end to end along the two grooves of actin filaments and provides stability to the filaments. The encoded protein is one type of alpha helical chain that forms the predominant tropomyosin of striated muscle, where it also functions in association with the troponin complex to regulate the calcium-dependent interaction of actin and myosin during muscle contraction. In smooth muscle and non-muscle cells, alternatively spliced transcript variants encoding a range of isoforms have been described. Mutations in this gene are associated with type 3 familial hypertrophic cardiomyopathy and dilated cardiomyopathy 1Y. [provided by RefSeq, Jun 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
Variant 15-63042789-C-T is Benign according to our data. Variant chr15-63042789-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 508349.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TPM1 | NM_001018005.2 | c.-41C>T | 5_prime_UTR_variant | 1/10 | ENST00000403994.9 | NP_001018005.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TPM1 | ENST00000403994.9 | c.-41C>T | 5_prime_UTR_variant | 1/10 | 1 | NM_001018005.2 | ENSP00000385107 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 7.06e-7 AC: 1AN: 1416498Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 705800
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74378
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 23, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at