rs387906699
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_000260.4(MYO7A):c.2011G>A(p.Gly671Ser) variant causes a missense change involving the alteration of a 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Consequence
MYO7A
NM_000260.4 missense
NM_000260.4 missense
Scores
15
3
1
Clinical Significance
Conservation
PhyloP100: 9.59
Genes affected
MYO7A (HGNC:7606): (myosin VIIA) This gene is a member of the myosin gene family. Myosins are mechanochemical proteins characterized by the presence of a motor domain, an actin-binding domain, a neck domain that interacts with other proteins, and a tail domain that serves as an anchor. This gene encodes an unconventional myosin with a very short tail. Defects in this gene are associated with the mouse shaker-1 phenotype and the human Usher syndrome 1B which are characterized by deafness, reduced vestibular function, and (in human) retinal degeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a hotspot region, there are 2 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 8 uncertain in NM_000260.4
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.979
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.2011G>A | p.Gly671Ser | missense_variant | 17/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.2011G>A | p.Gly671Ser | missense_variant | 17/49 | 1 | NM_000260.4 | ||
MYO7A | ENST00000458637.6 | c.2011G>A | p.Gly671Ser | missense_variant | 17/49 | 1 | P1 | ||
MYO7A | ENST00000409619.6 | c.1978G>A | p.Gly660Ser | missense_variant | 18/50 | 1 | |||
MYO7A | ENST00000409893.6 | c.76G>A | p.Gly26Ser | missense_variant | 1/11 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 34
GnomAD4 exome
Cov.:
34
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant nonsyndromic hearing loss 11 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jan 01, 2011 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 28, 2015 | The p.Gly671Ser variant in MYO7A has previously been reported in one Chinese ind ividual with dominant hearing loss (Sun 2011). The variant segregated with disea se in one affected relative, but additional affected family members were not tes ted (Sun 2011). The p.Gly671Ser variant has not been identified in large populat ion studies. Computational prediction tools and conservation analyses do not pro vide strong support for or against an impact to the protein. In summary, the cli nical significance of the p.Gly671Ser variant is uncertain. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Pathogenic
D;D;.;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
M;.;M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;D;.
REVEL
Pathogenic
Sift
Pathogenic
D;.;D;D;.
Sift4G
Pathogenic
D;D;D;D;.
Polyphen
D;.;.;.;.
Vest4
MutPred
Gain of phosphorylation at G671 (P = 0.0208);Gain of phosphorylation at G671 (P = 0.0208);Gain of phosphorylation at G671 (P = 0.0208);.;.;
MVP
MPC
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