rs397516293
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000260.4(MYO7A):āc.2122A>Gā(p.Met708Val) variant causes a missense change. The variant allele was found at a frequency of 0.00013 in 1,613,332 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.000098 ( 0 hom., cov: 33)
Exomes š: 0.00013 ( 2 hom. )
Consequence
MYO7A
NM_000260.4 missense
NM_000260.4 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 7.05
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 Benign. Variant got -9 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0311414).
BP6
Variant 11-77175399-A-G is Benign according to our data. Variant chr11-77175399-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 43173.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=4, Uncertain_significance=5}.
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.2122A>G | p.Met708Val | missense_variant | 18/49 | ENST00000409709.9 | NP_000251.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.2122A>G | p.Met708Val | missense_variant | 18/49 | 1 | NM_000260.4 | ENSP00000386331.3 | ||
MYO7A | ENST00000458637.6 | c.2122A>G | p.Met708Val | missense_variant | 18/49 | 1 | ENSP00000392185.2 | |||
MYO7A | ENST00000409619.6 | c.2089A>G | p.Met697Val | missense_variant | 19/50 | 1 | ENSP00000386635.2 | |||
MYO7A | ENST00000670577.1 | n.-39A>G | upstream_gene_variant | ENSP00000499323.1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152172Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000237 AC: 59AN: 249002Hom.: 1 AF XY: 0.000355 AC XY: 48AN XY: 135174
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GnomAD4 exome AF: 0.000133 AC: 195AN: 1461042Hom.: 2 Cov.: 31 AF XY: 0.000188 AC XY: 137AN XY: 726812
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GnomAD4 genome AF: 0.0000985 AC: 15AN: 152290Hom.: 0 Cov.: 33 AF XY: 0.000134 AC XY: 10AN XY: 74448
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:5Benign:4
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 27, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | MYO7A: BP4 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 05, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 21, 2024 | - - |
Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 20, 2017 | - - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | May 18, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 05, 2010 | Met708Val in exon 18 of MYO7A: This variant is not expected to have clinical sig nificance because this residue is not highly conserved across species. In additi on, computational analyses (PolyPhen, SIFT, AlignGVGD) do not suggest a high lik elihood of clinical significance. - |
Autosomal dominant nonsyndromic hearing loss 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 14, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N;.;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;.
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;.
Sift4G
Uncertain
D;D;D;D;.
Polyphen
B;.;.;.;.
Vest4
MutPred
Loss of catalytic residue at M708 (P = 0.1364);Loss of catalytic residue at M708 (P = 0.1364);Loss of catalytic residue at M708 (P = 0.1364);.;.;
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