chr22-36295593-G-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2
The NM_002473.6(MYH9):āc.3397C>Gā(p.Gln1133Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000235 in 1,613,866 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).
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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.3397C>G | p.Gln1133Glu | missense_variant | Exon 26 of 41 | ENST00000216181.11 | NP_002464.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.3397C>G | p.Gln1133Glu | missense_variant | Exon 26 of 41 | 1 | NM_002473.6 | ENSP00000216181.6 | ||
MYH9 | ENST00000685801.1 | c.3460C>G | p.Gln1154Glu | missense_variant | Exon 27 of 42 | ENSP00000510688.1 | ||||
MYH9 | ENST00000459960.1 | n.606C>G | non_coding_transcript_exon_variant | Exon 2 of 2 | 2 | |||||
MYH9 | ENST00000691109.1 | n.3692C>G | non_coding_transcript_exon_variant | Exon 20 of 35 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000279 AC: 7AN: 251146Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135824
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461722Hom.: 0 Cov.: 35 AF XY: 0.0000220 AC XY: 16AN XY: 727156
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74330
ClinVar
Submissions by phenotype
not specified Uncertain:1
The p.Gln1133Glu variant in MYH9 has not been previously reported in individuals with hearing loss. This variant has been identified in 2/33578 Latino chromosom es and 5/111576 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs368797590). Although this variant has been seen in the general population, its frequency is not high enough to rule o ut a pathogenic role. Computational prediction tools and conservation analysis s uggest that the p.Gln1133Glu variant may not impact the protein, though this inf ormation is not predictive enough to rule out pathogenicity. In summary, the cli nical significance of the p.Gln1133Glu variant is uncertain. ACMG/AMP Criteria a pplied: PM2; BP4. -
Autosomal dominant nonsyndromic hearing loss 17;C5200934:Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Uncertain:1
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Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Uncertain:1
The MYH9 c.3397C>G (p.Gln1133Glu) missense change has a maximum subpopulation frequency of 0.0058% in gnomAD v2.1.1(https://gnomad.broadinstitute.org/ ). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with MYH9-related disease. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. -
not provided Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at