rs779568205
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_006790.3(MYOT):c.398C>T(p.Pro133Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,613,928 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_006790.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYOT | NM_006790.3 | c.398C>T | p.Pro133Leu | missense_variant | Exon 3 of 10 | ENST00000239926.9 | NP_006781.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOT | ENST00000239926.9 | c.398C>T | p.Pro133Leu | missense_variant | Exon 3 of 10 | 1 | NM_006790.3 | ENSP00000239926.4 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000795 AC: 20AN: 251424Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135882
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461804Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727208
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74308
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 26, 2024 | The c.398C>T (p.P133L) alteration is located in exon 3 (coding exon 2) of the MYOT gene. This alteration results from a C to T substitution at nucleotide position 398, causing the proline (P) at amino acid position 133 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Myofibrillar myopathy 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 03, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 133 of the MYOT protein (p.Pro133Leu). This variant is present in population databases (rs779568205, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MYOT-related conditions. ClinVar contains an entry for this variant (Variation ID: 533010). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Heart failure Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Aug 03, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at