rs375955867
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BS1_SupportingBS2
The NM_002473.6(MYH9):c.4050G>C(p.Glu1350Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,609,316 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. E1350E) has been classified as Likely benign.
Frequency
Consequence
NM_002473.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.4050G>C | p.Glu1350Asp | missense_variant | 30/41 | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.4050G>C | p.Glu1350Asp | missense_variant | 30/41 | 1 | NM_002473.6 | P1 | |
MYH9 | ENST00000685801.1 | c.4113G>C | p.Glu1371Asp | missense_variant | 31/42 | ||||
MYH9 | ENST00000691109.1 | n.4345G>C | non_coding_transcript_exon_variant | 24/35 |
Frequencies
GnomAD3 genomes ? AF: 0.0000592 AC: 9AN: 152128Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000361 AC: 9AN: 249300Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134802
GnomAD4 exome AF: 0.0000206 AC: 30AN: 1457188Hom.: 0 Cov.: 33 AF XY: 0.0000207 AC XY: 15AN XY: 724958
GnomAD4 genome ? AF: 0.0000592 AC: 9AN: 152128Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74316
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2021 | 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 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jan 18, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 25, 2016 | The p.Glu1350Asp variant in MYH9 has not been previously reported in individuals with hearing loss. It has been identified in 4/66412 European chromosomes by th e Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs37 5955867). Although this variant has been seen in the general population, its fre quency is not high enough to rule out a pathogenic role. Computational predictio n tools and conservation analyses do not provide strong support for or against a n impact to the protein. In summary, the clinical significance of the p.Glu1350A sp variant is uncertain. - |
Autosomal dominant nonsyndromic hearing loss 17;C5200934:Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 06, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at