rs112597191
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS1
The NM_004999.4(MYO6):āc.2517T>Cā(p.Gly839=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,613,744 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 0.0014 ( 1 hom., cov: 32)
Exomes š: 0.00015 ( 0 hom. )
Consequence
MYO6
NM_004999.4 synonymous
NM_004999.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.32
Genes affected
MYO6 (HGNC:7605): (myosin VI) This gene encodes a reverse-direction motor protein that moves toward the minus end of actin filaments and plays a role in intracellular vesicle and organelle transport. The protein consists of a motor domain containing an ATP- and an actin-binding site and a globular tail which interacts with other proteins. This protein maintains the structural integrity of inner ear hair cells and mutations in this gene cause non-syndromic autosomal dominant and recessive hearing loss. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.7).
BP6
Variant 6-75886853-T-C is Benign according to our data. Variant chr6-75886853-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 259605.We mark this variant Likely_benign, oryginal submissions are: {Benign=3, Likely_benign=3, Uncertain_significance=1}.
BP7
Synonymous conserved (PhyloP=-1.32 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00135 (206/152260) while in subpopulation AFR AF= 0.00465 (193/41548). AF 95% confidence interval is 0.00411. There are 1 homozygotes in gnomad4. There are 94 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO6 | NM_004999.4 | c.2517T>C | p.Gly839= | synonymous_variant | 25/35 | ENST00000369977.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO6 | ENST00000369977.8 | c.2517T>C | p.Gly839= | synonymous_variant | 25/35 | 1 | NM_004999.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.00131 AC: 200AN: 152142Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000442 AC: 111AN: 251322Hom.: 1 AF XY: 0.000361 AC XY: 49AN XY: 135854
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GnomAD4 exome AF: 0.000154 AC: 225AN: 1461484Hom.: 0 Cov.: 31 AF XY: 0.000153 AC XY: 111AN XY: 727062
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GnomAD4 genome AF: 0.00135 AC: 206AN: 152260Hom.: 1 Cov.: 32 AF XY: 0.00126 AC XY: 94AN XY: 74458
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:6
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 23, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | MYO6: BP4, BP7 - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 07, 2023 | - - |
Autosomal recessive nonsyndromic hearing loss 37 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal dominant nonsyndromic hearing loss 22 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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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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