rs727504965
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2
The NM_001145809.2(MYH14):c.4152G>A(p.Glu1384=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000451 in 1,551,824 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000043 ( 0 hom. )
Consequence
MYH14
NM_001145809.2 synonymous
NM_001145809.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.59
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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 19-50280245-G-A is Benign according to our data. Variant chr19-50280245-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 179582.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}. Variant chr19-50280245-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=1.59 with no splicing effect.
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| MYH14 | NM_001145809.2 | c.4152G>A | p.Glu1384= | synonymous_variant | 32/43 | ENST00000642316.2 | NP_001139281.1 | |
| MYH14 | NM_001077186.2 | c.4053G>A | p.Glu1351= | synonymous_variant | 31/42 | NP_001070654.1 | ||
| MYH14 | NM_024729.4 | c.4029G>A | p.Glu1343= | synonymous_variant | 30/41 | NP_079005.3 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| MYH14 | ENST00000642316.2 | c.4152G>A | p.Glu1384= | synonymous_variant | 32/43 | NM_001145809.2 | ENSP00000493594 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000192 AC: 3AN: 156430Hom.: 0 AF XY: 0.0000242 AC XY: 2AN XY: 82578
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GnomAD4 exome AF: 0.00000429 AC: 6AN: 1399618Hom.: 0 Cov.: 32 AF XY: 0.00000579 AC XY: 4AN XY: 690328
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GnomAD4 genome 0.00000657 AC: 1AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 4A Uncertain:1
| Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
| Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 11, 2014 | Glu1384Glu in Exon 32 of MYH14: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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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