chr3-46858026-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000258.3(MYL3):c.*89G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 640,720 control chromosomes in the GnomAD database, including 11,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.18 ( 3313 hom., cov: 31)
Exomes 𝑓: 0.15 ( 7714 hom. )
Consequence
MYL3
NM_000258.3 3_prime_UTR
NM_000258.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.05
Genes affected
MYL3 (HGNC:7584): (myosin light chain 3) MYL3 encodes myosin light chain 3, an alkali light chain also referred to in the literature as both the ventricular isoform and the slow skeletal muscle isoform. Mutations in MYL3 have been identified as a cause of mid-left ventricular chamber type hypertrophic cardiomyopathy. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
Variant 3-46858026-C-T is Benign according to our data. Variant chr3-46858026-C-T is described in ClinVar as [Benign]. Clinvar id is 345568.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46858026-C-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYL3 | NM_000258.3 | c.*89G>A | 3_prime_UTR_variant | 7/7 | ENST00000292327.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYL3 | ENST00000292327.6 | c.*89G>A | 3_prime_UTR_variant | 7/7 | 1 | NM_000258.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.183 AC: 27741AN: 151872Hom.: 3310 Cov.: 31
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GnomAD4 exome AF: 0.152 AC: 74412AN: 488730Hom.: 7714 Cov.: 6 AF XY: 0.164 AC XY: 42339AN XY: 258580
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GnomAD4 genome AF: 0.183 AC: 27780AN: 151990Hom.: 3313 Cov.: 31 AF XY: 0.187 AC XY: 13912AN XY: 74280
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Hypertrophic cardiomyopathy 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at