rs769668877
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_016599.5(MYOZ2):āc.504T>Cā(p.Pro168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,613,970 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 Likely benign (ā ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 31)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
MYOZ2
NM_016599.5 synonymous
NM_016599.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.199
Genes affected
MYOZ2 (HGNC:1330): (myozenin 2) The protein encoded by this gene belongs to a family of sarcomeric proteins that bind to calcineurin, a phosphatase involved in calcium-dependent signal transduction in diverse cell types. These family members tether calcineurin to alpha-actinin at the z-line of the sarcomere of cardiac and skeletal muscle cells, and thus they are important for calcineurin signaling. Mutations in this gene cause cardiomyopathy familial hypertrophic type 16, a hereditary heart disorder. [provided by RefSeq, Aug 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 4-119164338-T-C is Benign according to our data. Variant chr4-119164338-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 227712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.199 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOZ2 | NM_016599.5 | c.504T>C | p.Pro168= | synonymous_variant | 5/6 | ENST00000307128.6 | |
MYOZ2 | XM_006714234.5 | c.504T>C | p.Pro168= | synonymous_variant | 5/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOZ2 | ENST00000307128.6 | c.504T>C | p.Pro168= | synonymous_variant | 5/6 | 1 | NM_016599.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251210Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135780
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461800Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727198
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152170Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74334
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 28, 2015 | p.Pro168Pro in exon 5 of MYOZ2: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 1/10270 African ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org). - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2022 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 25, 2020 | 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. - |
Computational scores
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Name
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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