rs782023308
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 6P and 3B. PM1PM2PM5BP4_ModerateBP6
The NM_000260.4(MYO7A):āc.1543A>Cā(p.Lys515Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000992 in 1,551,642 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). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K515N) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000260.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.1543A>C | p.Lys515Gln | missense_variant | 13/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.1543A>C | p.Lys515Gln | missense_variant | 13/49 | 1 | NM_000260.4 | ||
MYO7A | ENST00000458637.6 | c.1543A>C | p.Lys515Gln | missense_variant | 13/49 | 1 | P1 | ||
MYO7A | ENST00000409619.6 | c.1510A>C | p.Lys504Gln | missense_variant | 14/50 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000301 AC: 47AN: 156152Hom.: 1 AF XY: 0.000460 AC XY: 38AN XY: 82602
GnomAD4 exome AF: 0.000106 AC: 148AN: 1399330Hom.: 1 Cov.: 31 AF XY: 0.000168 AC XY: 116AN XY: 690170
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.0000806 AC XY: 6AN XY: 74474
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 08, 2014 | The Lys515Gln variant in MYO7A has been reported in one Usher syndrome study whe re it was detected in 1/878 (0.1%) control chromosomes and was classified as a " probably neutral" variant (Le Quesne Stabej 2012). This variant was absent from other large population studies. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the Lys515Gln variant is uncertain. - |
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;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Jan 11, 2017 | - - |
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. - |
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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at