rs61731838
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_001145809.2(MYH14):c.1755C>T(p.Gly585=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0665 in 1,613,792 control chromosomes in the GnomAD database, including 4,603 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.073 ( 529 hom., cov: 32)
Exomes 𝑓: 0.066 ( 4074 hom. )
Consequence
MYH14
NM_001145809.2 synonymous
NM_001145809.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.293
Genes affected
MYH14 (HGNC:23212): (myosin heavy chain 14) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.24).
BP6
Variant 19-50250613-C-T is Benign according to our data. Variant chr19-50250613-C-T is described in ClinVar as [Benign]. Clinvar id is 44050.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50250613-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.293 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.1755C>T | p.Gly585= | synonymous_variant | 15/43 | ENST00000642316.2 | NP_001139281.1 | |
MYH14 | NM_001077186.2 | c.1755C>T | p.Gly585= | synonymous_variant | 15/42 | NP_001070654.1 | ||
MYH14 | NM_024729.4 | c.1731C>T | p.Gly577= | synonymous_variant | 14/41 | NP_079005.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.1755C>T | p.Gly585= | synonymous_variant | 15/43 | NM_001145809.2 | ENSP00000493594 |
Frequencies
GnomAD3 genomes AF: 0.0725 AC: 11023AN: 152084Hom.: 522 Cov.: 32
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GnomAD3 exomes AF: 0.0844 AC: 20990AN: 248698Hom.: 1425 AF XY: 0.0780 AC XY: 10539AN XY: 135046
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GnomAD4 exome AF: 0.0659 AC: 96315AN: 1461590Hom.: 4074 Cov.: 31 AF XY: 0.0647 AC XY: 47036AN XY: 727080
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GnomAD4 genome AF: 0.0726 AC: 11053AN: 152202Hom.: 529 Cov.: 32 AF XY: 0.0747 AC XY: 5558AN XY: 74402
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 07, 2012 | Gly585Gly in Exon 15 of MYH14: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 6.9% (252/3668) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs61731838). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 25, 2017 | 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. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 31, 2024 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Autosomal dominant nonsyndromic hearing loss 4A 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