rs200115559
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_003803.4(MYOM1):c.1901-14T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 1,612,210 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0025 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00029 ( 2 hom. )
Consequence
MYOM1
NM_003803.4 splice_polypyrimidine_tract, intron
NM_003803.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.332
Genes affected
MYOM1 (HGNC:7613): (myomesin 1) The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD (myomesin 1) and 165 kD (myomesin 2). This protein, myomesin 1, like myomesin 2, titin, and other myofibrillar proteins contains structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin 1 and myomesin 2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. The integrating structure of the sarcomere arises from muscle-specific members of the superfamily of immunoglobulin-like proteins. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 18-3142077-A-G is Benign according to our data. Variant chr18-3142077-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 227691.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOM1 | NM_003803.4 | c.1901-14T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000356443.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.1901-14T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_003803.4 | P2 | |||
MYOM1 | ENST00000261606.11 | c.1901-14T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00243 AC: 369AN: 152156Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000695 AC: 172AN: 247456Hom.: 1 AF XY: 0.000410 AC XY: 55AN XY: 134302
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GnomAD4 exome AF: 0.000288 AC: 421AN: 1459936Hom.: 2 Cov.: 30 AF XY: 0.000233 AC XY: 169AN XY: 726110
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GnomAD4 genome ? AF: 0.00246 AC: 374AN: 152274Hom.: 2 Cov.: 32 AF XY: 0.00220 AC XY: 164AN XY: 74448
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 21, 2015 | c.1901-14T>C in intron 13 of MYOM1: This variant is not expected to have clinica l significance because it has been identified in 0.9% (88/9656) of African chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs200115559). - |
Hypertrophic cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
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