rs149271663
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_002473.6(MYH9):c.4479G>A(p.Ala1493=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,613,856 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 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000064 ( 0 hom. )
Consequence
MYH9
NM_002473.6 synonymous
NM_002473.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.93
Genes affected
MYH9 (HGNC:7579): (myosin heavy chain 9) This gene encodes a conventional non-muscle myosin; this protein should not be confused with the unconventional myosin-9a or 9b (MYO9A or MYO9B). The encoded protein is a myosin IIA heavy chain that contains an IQ domain and a myosin head-like domain which is involved in several important functions, including cytokinesis, cell motility and maintenance of cell shape. Defects in this gene have been associated with non-syndromic sensorineural deafness autosomal dominant type 17, Epstein syndrome, Alport syndrome with macrothrombocytopenia, Sebastian syndrome, Fechtner syndrome and macrothrombocytopenia with progressive sensorineural deafness. [provided by RefSeq, Dec 2011]
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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=-0.49).
BP6
?
Variant 22-36289163-C-T is Benign according to our data. Variant chr22-36289163-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 164433.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-3.93 with no splicing effect.
BS2
?
High AC in GnomAd at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.4479G>A | p.Ala1493= | synonymous_variant | 32/41 | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.4479G>A | p.Ala1493= | synonymous_variant | 32/41 | 1 | NM_002473.6 | P1 | |
MYH9 | ENST00000685801.1 | c.4542G>A | p.Ala1514= | synonymous_variant | 33/42 | ||||
MYH9 | ENST00000691109.1 | n.4774G>A | non_coding_transcript_exon_variant | 26/35 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152256Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251086Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135780
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GnomAD4 exome AF: 0.0000636 AC: 93AN: 1461600Hom.: 0 Cov.: 34 AF XY: 0.0000578 AC XY: 42AN XY: 727134
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152256Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74384
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | Ala1493Ala in Exon 32 of MYH9: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1/7020 European Ameri can chromosomes from a broad population by the NHLBI Exome Sequencing Project (h ttp://evs.gs.washington.edu/EVS; dbSNP rs149271663). - |
Autosomal dominant nonsyndromic hearing loss 17;C5200934:Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 02, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 22, 2022 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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