15-63059488-A-G
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000403994.9(TPM1):c.375-75A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.811 in 1,199,598 control chromosomes in the GnomAD database, including 395,949 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.81 ( 50279 hom., cov: 33)
Exomes 𝑓: 0.81 ( 345670 hom. )
Consequence
TPM1
ENST00000403994.9 intron
ENST00000403994.9 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.06
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
Variant 15-63059488-A-G is Benign according to our data. Variant chr15-63059488-A-G is described in ClinVar as [Benign]. Clinvar id is 1290395.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-63059488-A-G is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TPM1 | NM_001018005.2 | c.375-75A>G | intron_variant | ENST00000403994.9 | NP_001018005.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TPM1 | ENST00000403994.9 | c.375-75A>G | intron_variant | 1 | NM_001018005.2 | ENSP00000385107 | A1 |
Frequencies
GnomAD3 genomes AF: 0.811 AC: 123310AN: 152078Hom.: 50219 Cov.: 33
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GnomAD4 exome AF: 0.811 AC: 849181AN: 1047402Hom.: 345670 AF XY: 0.811 AC XY: 436792AN XY: 538440
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GnomAD4 genome AF: 0.811 AC: 123429AN: 152196Hom.: 50279 Cov.: 33 AF XY: 0.812 AC XY: 60424AN XY: 74398
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
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