rs141995460
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001145809.2(MYH14):āc.4486C>Gā(p.Gln1496Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,612,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.000013 ( 0 hom., cov: 33)
Exomes š: 0.0000068 ( 0 hom. )
Consequence
MYH14
NM_001145809.2 missense
NM_001145809.2 missense
Scores
2
11
Clinical Significance
Conservation
PhyloP100: 4.68
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 -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.17031577).
BS2
?
High AC in GnomAdExome4 at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.4486C>G | p.Gln1496Glu | missense_variant | 33/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.4387C>G | p.Gln1463Glu | missense_variant | 32/42 | ||
MYH14 | NM_024729.4 | c.4363C>G | p.Gln1455Glu | missense_variant | 31/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.4486C>G | p.Gln1496Glu | missense_variant | 33/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152250Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000289 AC: 7AN: 242458Hom.: 0 AF XY: 0.0000301 AC XY: 4AN XY: 132922
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GnomAD4 exome AF: 0.00000685 AC: 10AN: 1460320Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6AN XY: 726444
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152368Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74514
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
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 | Jun 05, 2014 | The Gln1496Glu variant in MYH14 has not been previously reported in individuals with hearing loss, but it has been identified in 0.52% (1/192) of Luhya (Kenya) chromosomes by the 1000 Genomes Project (dbSNP rs141995460). Although this varia nt has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation anal yses suggest that the Gln1496Glu variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the Gln1496Glu variant is uncertain. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 25, 2023 | The c.4363C>G (p.Q1455E) alteration is located in exon 31 (coding exon 30) of the MYH14 gene. This alteration results from a C to G substitution at nucleotide position 4363, causing the glutamine (Q) at amino acid position 1455 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;.;T;T;T
Polyphen
B;.;B;P;P;P;P;.
Vest4
MVP
MPC
0.28
ClinPred
T
GERP RS
Varity_R
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