rs727504861
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_002473.6(MYH9):c.1056C>T(p.Ile352=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,008 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000035 ( 1 hom. )
Consequence
MYH9
NM_002473.6 synonymous
NM_002473.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.38
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 -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.51).
BP6
Variant 22-36319592-G-A is Benign according to our data. Variant chr22-36319592-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 179427.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-1.38 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000329 (5/152126) while in subpopulation SAS AF= 0.000415 (2/4824). AF 95% confidence interval is 0.000073. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.1056C>T | p.Ile352= | synonymous_variant | 10/41 | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.1056C>T | p.Ile352= | synonymous_variant | 10/41 | 1 | NM_002473.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152126Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000636 AC: 16AN: 251442Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135900
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GnomAD4 exome AF: 0.0000349 AC: 51AN: 1461882Hom.: 1 Cov.: 32 AF XY: 0.0000495 AC XY: 36AN XY: 727240
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152126Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74320
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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 | Dec 12, 2013 | Ile352Ile in exon 10 of MYH9: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and it is not located w ithin the splice consensus sequence. - |
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 | Dec 16, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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