rs569541375
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PP2PP3BP6BS1BS2
The NM_002473.6(MYH9):c.5107C>T(p.Arg1703Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000992 in 1,612,426 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R1703Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_002473.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.5107C>T | p.Arg1703Trp | missense_variant | 36/41 | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.5107C>T | p.Arg1703Trp | missense_variant | 36/41 | 1 | NM_002473.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 151574Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000200 AC: 50AN: 250234Hom.: 0 AF XY: 0.000273 AC XY: 37AN XY: 135420
GnomAD4 exome AF: 0.000108 AC: 158AN: 1460734Hom.: 0 Cov.: 32 AF XY: 0.000133 AC XY: 97AN XY: 726724
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 151692Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2AN XY: 74120
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 21, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jun 15, 2021 | In silico analysis supports that this missense variant has a deleterious effect on 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 | Nov 25, 2013 | The Arg1703Trp variant in MYH9 has not been previously reported in individuals w ith hearing loss or in large population studies. Computational analyses (biochem ical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugges t that the Arg1703Trp variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, additional data i s needed to determine the clinical significance of this variant. - |
MYH9-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 05, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at