rs201839634
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001145809.2(MYH14):c.5778C>T(p.Leu1926=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000066 in 1,546,562 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 (★★).
Frequency
Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
MYH14
NM_001145809.2 synonymous
NM_001145809.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.21
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=-0.32).
BP6
Variant 19-50307148-C-T is Benign according to our data. Variant chr19-50307148-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 504621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=3.21 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000348 (53/152270) while in subpopulation AFR AF= 0.00123 (51/41550). AF 95% confidence interval is 0.000958. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 53 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.5778C>T | p.Leu1926= | synonymous_variant | 41/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.5679C>T | p.Leu1893= | synonymous_variant | 40/42 | ||
MYH14 | NM_024729.4 | c.5655C>T | p.Leu1885= | synonymous_variant | 39/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.5778C>T | p.Leu1926= | synonymous_variant | 41/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes AF: 0.000348 AC: 53AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000981 AC: 15AN: 152938Hom.: 0 AF XY: 0.000124 AC XY: 10AN XY: 80860
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GnomAD4 exome AF: 0.0000351 AC: 49AN: 1394292Hom.: 0 Cov.: 29 AF XY: 0.0000378 AC XY: 26AN XY: 687816
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GnomAD4 genome AF: 0.000348 AC: 53AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27AN XY: 74464
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ClinVar
Significance: Benign/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 | Jun 04, 2016 | p.Leu1926Leu in exon 41 of MYH14: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 4/2018 African chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs201839634). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 13, 2023 | - - |
MYH14-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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