15-63043711-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2
The ENST00000267996.11(TPM1):c.120G>A(p.Glu40=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000147 in 1,546,864 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 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 1 hom. )
Consequence
TPM1
ENST00000267996.11 synonymous
ENST00000267996.11 synonymous
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 5.27
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.33).
BP6
Variant 15-63043711-G-A is Benign according to our data. Variant chr15-63043711-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 43685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63043711-G-A is described in Lovd as [Likely_benign]. Variant chr15-63043711-G-A is described in Lovd as [Benign].
BS2
High AC in GnomAd4 at 26 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
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TPM1 | NM_001018005.2 | c.115-316G>A | intron_variant | ENST00000403994.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM1 | ENST00000403994.9 | c.115-316G>A | intron_variant | 1 | NM_001018005.2 | A1 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152234Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000197 AC: 28AN: 142146Hom.: 0 AF XY: 0.000144 AC XY: 11AN XY: 76284
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GnomAD4 exome AF: 0.000144 AC: 201AN: 1394512Hom.: 1 Cov.: 31 AF XY: 0.000138 AC XY: 95AN XY: 687814
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GnomAD4 genome AF: 0.000171 AC: 26AN: 152352Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74488
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:9
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | TPM1: BP4, BP7, BS1 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 09, 2011 | Glu40Glu in exon 1 of TPM1: This variant does not change an amino acid and does not affect the splice consensus sequence. This makes a disease causing role very unlikely. - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 24, 2018 | - - |
TPM1-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 21, 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). - |
Computational scores
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Benign
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RBP_binding_hub_radar
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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