rs4775613
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_001018005.2(TPM1):c.241-88G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 1,580,308 control chromosomes in the GnomAD database, including 246,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.52 ( 21038 hom., cov: 32)
Exomes 𝑓: 0.56 ( 225075 hom. )
Consequence
TPM1
NM_001018005.2 intron
NM_001018005.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.381
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=-0.82).
BP6
?
Variant 15-63056897-G-A is Benign according to our data. Variant chr15-63056897-G-A is described in ClinVar as [Benign]. Clinvar id is 1267396.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-63056897-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPM1 | NM_001018005.2 | c.241-88G>A | intron_variant | ENST00000403994.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPM1 | ENST00000403994.9 | c.241-88G>A | intron_variant | 1 | NM_001018005.2 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.520 AC: 78981AN: 151988Hom.: 21046 Cov.: 32
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GnomAD4 exome AF: 0.559 AC: 798181AN: 1428202Hom.: 225075 Cov.: 23 AF XY: 0.557 AC XY: 397076AN XY: 712530
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GnomAD4 genome ? AF: 0.519 AC: 78983AN: 152106Hom.: 21038 Cov.: 32 AF XY: 0.520 AC XY: 38640AN XY: 74360
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at