rs727505048
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004999.4(MYO6):āc.2716T>Cā(p.Ser906Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000186 in 1,612,988 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000014 ( 0 hom. )
Consequence
MYO6
NM_004999.4 missense
NM_004999.4 missense
Scores
5
12
Clinical Significance
Conservation
PhyloP100: 4.08
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO6 | NM_004999.4 | c.2716T>C | p.Ser906Pro | missense_variant | 26/35 | ENST00000369977.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO6 | ENST00000369977.8 | c.2716T>C | p.Ser906Pro | missense_variant | 26/35 | 1 | NM_004999.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000661 AC: 1AN: 151198Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461790Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727190
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GnomAD4 genome ? AF: 0.00000661 AC: 1AN: 151198Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 73714
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
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 | Apr 04, 2014 | The Ser906Pro variant in MYO6 has not been previously reported in individuals wi th hearing loss and was absent from large population studies. Computational pred iction tools and conservation analyses do not provide strong support for or agai nst an impact to the protein. In summary, additional information is needed to de termine the clinical significance of this variant. - |
Autosomal dominant nonsyndromic hearing loss 22 Uncertain:1
Uncertain significance, no assertion criteria provided | research | Division of Human Genetics, Children's Hospital of Philadelphia | Oct 27, 2015 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;.;.;.;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;.;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;.;N;.
REVEL
Benign
Sift
Benign
T;T;T;.;T;.
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.72
.;P;P;P;.;.
Vest4
MutPred
Loss of phosphorylation at S906 (P = 0.0172);Loss of phosphorylation at S906 (P = 0.0172);Loss of phosphorylation at S906 (P = 0.0172);Loss of phosphorylation at S906 (P = 0.0172);Loss of phosphorylation at S906 (P = 0.0172);Loss of phosphorylation at S906 (P = 0.0172);
MVP
MPC
0.33
ClinPred
D
GERP RS
gMVP
Splicing
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Calibrated prediction
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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