rs397517047
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_004999.4(MYO6):c.2548C>G(p.Leu850Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
MYO6
NM_004999.4 missense
NM_004999.4 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 4.80
Genes affected
MYO6 (HGNC:7605): (myosin VI) This gene encodes a reverse-direction motor protein that moves toward the minus end of actin filaments and plays a role in intracellular vesicle and organelle transport. The protein consists of a motor domain containing an ATP- and an actin-binding site and a globular tail which interacts with other proteins. This protein maintains the structural integrity of inner ear hair cells and mutations in this gene cause non-syndromic autosomal dominant and recessive hearing loss. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.31736368).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO6 | NM_004999.4 | c.2548C>G | p.Leu850Val | missense_variant | 25/35 | ENST00000369977.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO6 | ENST00000369977.8 | c.2548C>G | p.Leu850Val | missense_variant | 25/35 | 1 | NM_004999.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | Jul 28, 2010 | Variant classified as Uncertain Significance - Favor Benign. The Leu850Val varia nt in MYO6 has not been reported in the literature nor previously identified by our laboratory. This residue is conserved across mammals though not in lower spe cies; however, do not suggest a high likelihood of clinical significance. It sho uld be noted that this lab has only sequenced the MYO6 in 61 Caucasian individua ls such that the full spectrum of benign variation has not yet been defined for this gene, increasing the possibility that this may be a benign variant. In summ ary, the clinical significance of this variant cannot be determined with certain ty at this time; however based upon the arguments described above, we would lean towards a more likely benign role. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;.;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;N;.
REVEL
Uncertain
Sift
Benign
T;T;T;.;T;.
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.36, 0.23
.;B;B;B;.;.
Vest4
MutPred
Loss of stability (P = 0.0451);Loss of stability (P = 0.0451);Loss of stability (P = 0.0451);Loss of stability (P = 0.0451);Loss of stability (P = 0.0451);Loss of stability (P = 0.0451);
MVP
MPC
0.26
ClinPred
D
GERP RS
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