rs758626716
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 3P and 9B. PM1PP2BP6BS1BS2
The NM_002473.6(MYH9):c.4247C>T(p.Thr1416Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000818 in 1,614,042 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. T1416T) 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 -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.4247C>T | p.Thr1416Met | missense_variant | 31/41 | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.4247C>T | p.Thr1416Met | missense_variant | 31/41 | 1 | NM_002473.6 | P1 | |
MYH9 | ENST00000685801.1 | c.4310C>T | p.Thr1437Met | missense_variant | 32/42 | ||||
MYH9 | ENST00000691109.1 | n.4542C>T | non_coding_transcript_exon_variant | 25/35 |
Frequencies
GnomAD3 genomes ? AF: 0.0000985 AC: 15AN: 152240Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251370Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135902
GnomAD4 exome AF: 0.0000800 AC: 117AN: 1461802Hom.: 0 Cov.: 32 AF XY: 0.0000811 AC XY: 59AN XY: 727218
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152240Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74372
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 18, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 15, 2021 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published in relationship to MYH9-related disorders as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25752595) - |
Autosomal dominant nonsyndromic hearing loss 17 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 04, 2015 | The p.Thr1416Met variant in MYH9 has not been previously reported in individuals with hearing loss, but has been identified in 2/66686 European chromosomes by t he Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computat ional prediction tools and conservation analysis suggest that the variant may im pact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.Thr1416Met variant is uncertain. - |
MYH9-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at