rs116571790
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_004999.4(MYO6):c.2175A>G(p.Lys725=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,614,116 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00083 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000086 ( 0 hom. )
Consequence
MYO6
NM_004999.4 synonymous
NM_004999.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.16
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 -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
Variant 6-75879917-A-G is Benign according to our data. Variant chr6-75879917-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 504642.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.16 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000827 (126/152284) while in subpopulation AFR AF= 0.0027 (112/41544). AF 95% confidence interval is 0.00229. There are 0 homozygotes in gnomad4. There are 53 alleles in male gnomad4 subpopulation. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO6 | NM_004999.4 | c.2175A>G | p.Lys725= | synonymous_variant | 21/35 | ENST00000369977.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO6 | ENST00000369977.8 | c.2175A>G | p.Lys725= | synonymous_variant | 21/35 | 1 | NM_004999.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000828 AC: 126AN: 152166Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000243 AC: 61AN: 251462Hom.: 0 AF XY: 0.000191 AC XY: 26AN XY: 135902
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GnomAD4 exome AF: 0.0000855 AC: 125AN: 1461832Hom.: 0 Cov.: 32 AF XY: 0.0000866 AC XY: 63AN XY: 727222
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GnomAD4 genome ? AF: 0.000827 AC: 126AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.000712 AC XY: 53AN XY: 74450
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 19, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 01, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | p.Lys725Lys in Exon 21 of MYO6: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue, is not located withi n the splice consensus sequence, and has been identified in 0.2% (25/10396) of A frican American chromosomes by the Exome Aggregation Consortium (ExAC, http://ex ac.broadinstitute.org; dbSNP rs116571790). - |
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