4-119151032-A-G
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_016599.5(MYOZ2):c.237A>G(p.Ala79Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 1,610,914 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_016599.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MYOZ2 | NM_016599.5 | c.237A>G | p.Ala79Ala | synonymous_variant | Exon 3 of 6 | ENST00000307128.6 | NP_057683.1 | |
MYOZ2 | XM_006714234.5 | c.237A>G | p.Ala79Ala | synonymous_variant | Exon 3 of 6 | XP_006714297.1 | ||
LOC105379404 | XR_001741421.2 | n.-73T>C | upstream_gene_variant |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00931 AC: 1417AN: 152216Hom.: 5 Cov.: 32
GnomAD3 exomes AF: 0.00947 AC: 2377AN: 251068Hom.: 19 AF XY: 0.00997 AC XY: 1353AN XY: 135718
GnomAD4 exome AF: 0.0124 AC: 18126AN: 1458580Hom.: 143 Cov.: 33 AF XY: 0.0121 AC XY: 8817AN XY: 725858
GnomAD4 genome AF: 0.00930 AC: 1416AN: 152334Hom.: 5 Cov.: 32 AF XY: 0.00861 AC XY: 641AN XY: 74488
ClinVar
Submissions by phenotype
not specified Benign:4
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
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Hypertrophic cardiomyopathy 16 Benign:4
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not provided Benign:3Other:1
MYOZ2: BP4, BP7, BS1, BS2 -
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Variant summary: The MYOZ2 c.237A>G (p.Ala79Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may not affect binding of ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1202/121194 control chromosomes (9 homozygotes) from ExAC, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.014932 (995/66636). This frequency is about 597 times the estimated maximal expected allele frequency of a pathogenic MYOZ2 variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. In addition, multiple clinical diagnostic laboratories in ClinVar have classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals in literature. Taken together, this variant is classified as benign. -
Cardiomyopathy Benign:1
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Hypertrophic cardiomyopathy Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as 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. -
MYOZ2-related disorder Benign:1
This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at