rs190695624
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001145809.2(MYH14):c.5868C>T(p.Ala1956=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00892 in 1,613,836 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0069 ( 5 hom., cov: 31)
Exomes 𝑓: 0.0091 ( 82 hom. )
Consequence
MYH14
NM_001145809.2 synonymous
NM_001145809.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.87
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
?
Variant 19-50309085-C-T is Benign according to our data. Variant chr19-50309085-C-T is described in ClinVar as [Benign]. Clinvar id is 44076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50309085-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-3.87 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00685 (1043/152244) while in subpopulation NFE AF= 0.0108 (733/67996). AF 95% confidence interval is 0.0101. There are 5 homozygotes in gnomad4. There are 496 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 1043 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.5868C>T | p.Ala1956= | synonymous_variant | 42/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.5769C>T | p.Ala1923= | synonymous_variant | 41/42 | ||
MYH14 | NM_024729.4 | c.5745C>T | p.Ala1915= | synonymous_variant | 40/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.5868C>T | p.Ala1956= | synonymous_variant | 42/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes ? AF: 0.00686 AC: 1043AN: 152126Hom.: 5 Cov.: 31
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GnomAD3 exomes AF: 0.00782 AC: 1947AN: 248984Hom.: 13 AF XY: 0.00790 AC XY: 1068AN XY: 135108
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GnomAD4 exome AF: 0.00914 AC: 13355AN: 1461592Hom.: 82 Cov.: 33 AF XY: 0.00917 AC XY: 6665AN XY: 727098
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GnomAD4 genome ? AF: 0.00685 AC: 1043AN: 152244Hom.: 5 Cov.: 31 AF XY: 0.00666 AC XY: 496AN XY: 74432
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Ala1956Ala in Exon 42 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 1.0% (68/6808) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS). - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 16, 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. - |
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 22, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | MYH14: BP4, BP7, BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
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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Name
Calibrated prediction
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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