rs778312429
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2
The NM_001145809.2(MYH14):c.1174C>T(p.Arg392Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,613,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
MYH14
NM_001145809.2 missense
NM_001145809.2 missense
Scores
2
7
4
Clinical Significance
Conservation
PhyloP100: 1.46
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 Likely_benign. Variant got -3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.808
BS2
?
High AC in GnomAd4 at 7 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.1174C>T | p.Arg392Trp | missense_variant | 11/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.1174C>T | p.Arg392Trp | missense_variant | 11/42 | ||
MYH14 | NM_024729.4 | c.1150C>T | p.Arg384Trp | missense_variant | 10/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.1174C>T | p.Arg392Trp | missense_variant | 11/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000461 AC: 7AN: 152008Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000604 AC: 15AN: 248188Hom.: 0 AF XY: 0.0000816 AC XY: 11AN XY: 134788
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GnomAD4 exome AF: 0.000131 AC: 192AN: 1461608Hom.: 0 Cov.: 32 AF XY: 0.000124 AC XY: 90AN XY: 727090
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GnomAD4 genome ? AF: 0.0000461 AC: 7AN: 152008Hom.: 0 Cov.: 31 AF XY: 0.0000539 AC XY: 4AN XY: 74234
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 25, 2018 | The p.Arg392Trp variant in MYH14 has not been previously reported in individuals with hearing loss, but has been identified in 16/125774 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSN P rs778312429). Computational prediction tools and conservation analysis suggest that the p.Arg392Trp variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical sign ificance of the p.Arg392Trp variant is uncertain. ACMG/AMP Criteria applied: PP3 . - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Benign
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Pathogenic
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;.;D;D;D
Polyphen
D;D;D;D;.;D;D
Vest4
MutPred
0.46
.;.;Loss of disorder (P = 0.0081);.;.;.;Loss of disorder (P = 0.0081);
MVP
MPC
1.4
ClinPred
D
GERP RS
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gMVP
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