rs201178011
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_000260.4(MYO7A):c.2006G>A(p.Arg669Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000248 in 1,613,358 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R669G) has been classified as Uncertain significance.
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.2006G>A | p.Arg669Gln | missense_variant | 17/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.2006G>A | p.Arg669Gln | missense_variant | 17/49 | 1 | NM_000260.4 | ||
MYO7A | ENST00000458637.6 | c.2006G>A | p.Arg669Gln | missense_variant | 17/49 | 1 | P1 | ||
MYO7A | ENST00000409619.6 | c.1973G>A | p.Arg658Gln | missense_variant | 18/50 | 1 | |||
MYO7A | ENST00000409893.6 | c.71G>A | p.Arg24Gln | missense_variant | 1/11 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152230Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000930 AC: 23AN: 247274Hom.: 0 AF XY: 0.0000743 AC XY: 10AN XY: 134644
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461128Hom.: 0 Cov.: 34 AF XY: 0.0000165 AC XY: 12AN XY: 726816
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152230Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Dec 08, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 29, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 08, 2015 | The p.Arg669Gln variant in MYO7A has not been previously reported in individuals with hearing loss or Usher syndrome. This variant has been identified in 6/104 66 Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs201178011). Computational prediction tools and conserva tion analysis do not provide strong support for or against an impact to the prot ein. In summary, the clinical significance of the p.Arg669Gln variant is uncerta in. - |
Usher syndrome type 1;C1838701:Autosomal recessive nonsyndromic hearing loss 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Feb 21, 2017 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 12, 2021 | The c.2006G>A (p.R669Q) alteration is located in exon 17 (coding exon 16) of the MYO7A gene. This alteration results from a G to A substitution at nucleotide position 2006, causing the arginine (R) at amino acid position 669 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Usher syndrome type 1B Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 26, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at