4-119136526-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PVS1_SupportingPM2
The NM_016599.5(MYOZ2):c.1A>T(p.Met1?) variant causes a initiator codon change. The variant allele was found at a frequency of 0.00000124 in 1,613,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_016599.5 initiator_codon
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461024Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726792
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74370
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy Uncertain:1
This sequence change affects the initiator methionine of the MYOZ2 mRNA. The next in-frame methionine is located at codon 7. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYOZ2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
Cardiovascular phenotype Uncertain:1
The p.M1? variant (also known as c.1A>T) is located in coding exon 1 of the MYOZ2 gene and results from a A to T substitution at nucleotide position 1. This alters the methionine residue at the initiation codon (ATG). This amino acid position is highly conserved in available vertebrate species. Sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. However, the evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. -
Hypertrophic cardiomyopathy 16 Uncertain:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at