chr4-119135910-A-G
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_016599.5(MYOZ2):c.-87A>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 0.00949 in 160,594 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0095 ( 10 hom., cov: 32)
Exomes 𝑓: 0.0093 ( 2 hom. )
Consequence
MYOZ2
NM_016599.5 5_prime_UTR
NM_016599.5 5_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.270
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
BP6
?
Variant 4-119135910-A-G is Benign according to our data. Variant chr4-119135910-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 31785.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-119135910-A-G is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0095 (1447/152310) while in subpopulation SAS AF= 0.0313 (151/4826). AF 95% confidence interval is 0.0272. There are 10 homozygotes in gnomad4. There are 725 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 1447 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYOZ2 | NM_016599.5 | c.-87A>G | 5_prime_UTR_variant | 1/6 | ENST00000307128.6 | ||
MYOZ2 | XM_006714234.5 | c.-87A>G | 5_prime_UTR_variant | 1/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYOZ2 | ENST00000307128.6 | c.-87A>G | 5_prime_UTR_variant | 1/6 | 1 | NM_016599.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00951 AC: 1447AN: 152192Hom.: 10 Cov.: 32
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GnomAD4 exome AF: 0.00930 AC: 77AN: 8284Hom.: 2 Cov.: 0 AF XY: 0.0105 AC XY: 46AN XY: 4392
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1Other:1
not provided, no classification provided | curation | Leiden Muscular Dystrophy (MYOZ2) | Apr 20, 2012 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 08, 2019 | - - |
Computational scores
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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