rs28940306
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2PP3_ModeratePP5
The NM_001145809.2(MYH14):c.3049C>T(p.Leu1017Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 31)
Consequence
MYH14
NM_001145809.2 missense
NM_001145809.2 missense
Scores
3
7
3
Clinical Significance
Conservation
PhyloP100: 3.18
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 Uncertain_significance. Variant got 5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.883
PP5
?
Variant 19-50271424-C-T is Pathogenic according to our data. Variant chr19-50271424-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 2197.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr19-50271424-C-T is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH14 | NM_001145809.2 | c.3049C>T | p.Leu1017Phe | missense_variant | 25/43 | ENST00000642316.2 | |
MYH14 | NM_001077186.2 | c.2950C>T | p.Leu984Phe | missense_variant | 24/42 | ||
MYH14 | NM_024729.4 | c.2926C>T | p.Leu976Phe | missense_variant | 23/41 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH14 | ENST00000642316.2 | c.3049C>T | p.Leu1017Phe | missense_variant | 25/43 | NM_001145809.2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD3 exomes AF: 0.00000428 AC: 1AN: 233784Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 126566
GnomAD3 exomes
AF:
AC:
1
AN:
233784
Hom.:
AF XY:
AC XY:
0
AN XY:
126566
Gnomad AFR exome
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Gnomad ASJ exome
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Gnomad SAS exome
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Gnomad FIN exome
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Gnomad OTH exome
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GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ExAC
?
AF:
AC:
1
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 4A Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 01, 2004 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
A;A;A;A
PrimateAI
Uncertain
T
Sift4G
Uncertain
D;D;D;.;D;D;D
Polyphen
P;P;B;P;.;P;B
Vest4
MutPred
0.71
.;.;Gain of helix (P = 0.0861);.;.;.;Gain of helix (P = 0.0861);
MVP
MPC
0.44
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at