rs79149418
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003803.4(MYOM1):āc.2625T>Cā(p.Leu875=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,613,962 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00066 ( 1 hom., cov: 32)
Exomes š: 0.0010 ( 38 hom. )
Consequence
MYOM1
NM_003803.4 synonymous
NM_003803.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.600
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 18-3129401-A-G is Benign according to our data. Variant chr18-3129401-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 239571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.6 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000657 (100/152256) while in subpopulation EAS AF= 0.0182 (94/5172). AF 95% confidence interval is 0.0152. There are 1 homozygotes in gnomad4. There are 59 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 38 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOM1 | NM_003803.4 | c.2625T>C | p.Leu875= | synonymous_variant | 18/38 | ENST00000356443.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.2625T>C | p.Leu875= | synonymous_variant | 18/38 | 1 | NM_003803.4 | P2 | |
MYOM1 | ENST00000261606.11 | c.2506+1974T>C | intron_variant | 1 | A2 | ||||
MYOM1 | ENST00000582016.1 | n.181T>C | non_coding_transcript_exon_variant | 1/3 | 4 |
Frequencies
GnomAD3 genomes ? AF: 0.000657 AC: 100AN: 152138Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00138 AC: 343AN: 249252Hom.: 1 AF XY: 0.00135 AC XY: 183AN XY: 135214
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GnomAD4 exome AF: 0.00105 AC: 1532AN: 1461706Hom.: 38 Cov.: 31 AF XY: 0.00103 AC XY: 749AN XY: 727134
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GnomAD4 genome ? AF: 0.000657 AC: 100AN: 152256Hom.: 1 Cov.: 32 AF XY: 0.000793 AC XY: 59AN XY: 74446
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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 | Ambry Genetics | Mar 25, 2022 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Hypertrophic cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
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