chr4-119136523-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2BP4_StrongBS2
The NM_016599.5(MYOZ2):c.-3A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_016599.5 5_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460956Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 726760
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.-3A>G variant in MYOZ2 has not been previously reported in individuals wit h cardiomyopathy and was absent from large population studies. This variant is l ocated in the 5' UTR and is part of the translation initiation (Kozak) sequence, but its effect on translation is unknown. In summary, while the clinical signif icance of the c.-3A>G variant is uncertain. -
Cardiovascular phenotype Uncertain:1
The c.-3A>G variant is located in the 5' untranslated region (5’ UTR) of the MYOZ2 gene. This variant results from an A to G substitution 3 bases upstream from the first translated codon. This variant was previously reported in the SNPDatabase as rs372377840. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This nucleotide position is not well conserved in available vertebrate species, and G is the reference nucleotide in six species. Since supporting evidence for this variant is limited at this time, the clinical significance of this variant remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at