rs373656667
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_000260.4(MYO7A):āc.2181T>Cā(p.Phe727=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000252 in 1,613,202 control chromosomes in the GnomAD database, including 1 homozygotes. 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: š 0.00030 ( 0 hom., cov: 33)
Exomes š: 0.00025 ( 1 hom. )
Consequence
MYO7A
NM_000260.4 synonymous
NM_000260.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.507
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 -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.61).
BP6
?
Variant 11-77175458-T-C is Benign according to our data. Variant chr11-77175458-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 227679.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1, Likely_benign=4}. Variant chr11-77175458-T-C is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.507 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.2181T>C | p.Phe727= | synonymous_variant | 18/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.2181T>C | p.Phe727= | synonymous_variant | 18/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000296 AC: 45AN: 152196Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000362 AC: 90AN: 248900Hom.: 0 AF XY: 0.000377 AC XY: 51AN XY: 135124
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GnomAD4 exome AF: 0.000248 AC: 362AN: 1460888Hom.: 1 Cov.: 31 AF XY: 0.000275 AC XY: 200AN XY: 726744
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GnomAD4 genome ? AF: 0.000295 AC: 45AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.000269 AC XY: 20AN XY: 74480
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:5
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:3
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | MYO7A: BP4, BP7 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2020 | - - |
Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Usher syndrome type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 05, 2016 | p.Phe727Phe in Exon 18 of MYO7A: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 36/66208 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org). - |
Autosomal dominant nonsyndromic hearing loss 11 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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