rs558991834
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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.1155C>T(p.Asn385=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,613,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00022 ( 1 hom., cov: 31)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
MYH14
NM_001145809.2 synonymous
NM_001145809.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.34
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=-0.46).
BP6
Variant 19-50244282-C-T is Benign according to our data. Variant chr19-50244282-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227573.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=3.34 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000217 (33/152236) while in subpopulation AMR AF= 0.00196 (30/15276). AF 95% confidence interval is 0.00141. There are 1 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 33 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.1155C>T | p.Asn385= | synonymous_variant | 11/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.1155C>T | p.Asn385= | synonymous_variant | 11/42 | ||
MYH14 | NM_024729.4 | c.1131C>T | p.Asn377= | synonymous_variant | 10/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.1155C>T | p.Asn385= | synonymous_variant | 11/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes AF: 0.000217 AC: 33AN: 152118Hom.: 1 Cov.: 31
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GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248730Hom.: 0 AF XY: 0.0000444 AC XY: 6AN XY: 134996
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GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461670Hom.: 0 Cov.: 32 AF XY: 0.0000248 AC XY: 18AN XY: 727118
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GnomAD4 genome AF: 0.000217 AC: 33AN: 152236Hom.: 1 Cov.: 31 AF XY: 0.000228 AC XY: 17AN XY: 74438
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 06, 2015 | p.Asn385Asn in Exon 11 of MYH14: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 1/9780 of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org). - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 18, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 13, 2022 | - - |
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