11-77166091-G-A
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_ModerateBP6BS1
The NM_000260.4(MYO7A):c.1726G>A(p.Asp576Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000775 in 1,613,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
MYO7A
NM_000260.4 missense
NM_000260.4 missense
Scores
6
6
7
Clinical Significance
Conservation
PhyloP100: 6.92
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_benign. Variant got -5 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.11430189).
BP6
Variant 11-77166091-G-A is Benign according to our data. Variant chr11-77166091-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 164674.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=1, Benign=1}.
BS1
Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.0000445 (65/1461634) while in subpopulation AFR AF= 0.00167 (56/33474). AF 95% confidence interval is 0.00132. There are 0 homozygotes in gnomad4_exome. There are 24 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.1726G>A | p.Asp576Asn | missense_variant | 15/49 | 1 | NM_000260.4 | ENSP00000386331.3 | ||
MYO7A | ENST00000458637.6 | c.1726G>A | p.Asp576Asn | missense_variant | 15/49 | 1 | ENSP00000392185.2 | |||
MYO7A | ENST00000409619.6 | c.1693G>A | p.Asp565Asn | missense_variant | 16/50 | 1 | ENSP00000386635.2 | |||
MYO7A | ENST00000669443.1 | c.34G>A | p.Asp12Asn | missense_variant | 1/3 | ENSP00000499530.1 |
Frequencies
GnomAD3 genomes AF: 0.000401 AC: 61AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000108 AC: 27AN: 249102Hom.: 0 AF XY: 0.0000814 AC XY: 11AN XY: 135158
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GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461634Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727088
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GnomAD4 genome AF: 0.000394 AC: 60AN: 152280Hom.: 0 Cov.: 32 AF XY: 0.000416 AC XY: 31AN XY: 74446
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 06, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Asp576Asn varia nt in MYO7A has not been previously reported in individuals with hearing loss, b ut has been identified in 0.1% (4/4022) of African American chromosomes by the N HLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs187165 412). Although this variant has been seen in the general population, its frequen cy is not high enough to rule out a pathogenic role. Computational analyses (bi ochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) d o not provide strong support for or against an impact to the protein. In summary , additional information is needed to determine the clinical significance of th is variant.. - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 28, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 21, 2025 | - - |
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Apr 20, 2017 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Pathogenic
DEOGEN2
Pathogenic
D;T;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L;.;L;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;D;D
REVEL
Uncertain
Sift
Benign
D;.;D;D
Sift4G
Uncertain
T;T;T;T
Polyphen
D;.;.;.
Vest4
MVP
MPC
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