rs121913656
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP2PP3_ModeratePP5_Moderate
The NM_002473.6(MYH9):c.3464C>T(p.Thr1155Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1155A) has been classified as Pathogenic.
Frequency
Consequence
NM_002473.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH9 | NM_002473.6 | c.3464C>T | p.Thr1155Ile | missense_variant | 26/41 | ENST00000216181.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH9 | ENST00000216181.11 | c.3464C>T | p.Thr1155Ile | missense_variant | 26/41 | 1 | NM_002473.6 | P1 | |
MYH9 | ENST00000685801.1 | c.3527C>T | p.Thr1176Ile | missense_variant | 27/42 | ||||
MYH9 | ENST00000459960.1 | n.673C>T | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
MYH9 | ENST00000691109.1 | n.3759C>T | non_coding_transcript_exon_variant | 20/35 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2022 | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 14077). This missense change has been observed in individual(s) with MYH9-related disorders (PMID: 10973260, 12792306; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 1155 of the MYH9 protein (p.Thr1155Ile). - |
Macrothrombocytopenia and granulocyte inclusions with or without nephritis or sensorineural hearing loss Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2003 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at