22-25763234-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032608.7(MYO18B):c.43C>T(p.Arg15Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000995 in 1,607,960 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R15Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_032608.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO18B | NM_032608.7 | c.43C>T | p.Arg15Trp | missense_variant | 3/44 | ENST00000335473.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO18B | ENST00000335473.12 | c.43C>T | p.Arg15Trp | missense_variant | 3/44 | 1 | NM_032608.7 | A2 | |
MYO18B | ENST00000407587.6 | c.43C>T | p.Arg15Trp | missense_variant | 3/44 | 1 | P5 | ||
MYO18B | ENST00000536101.5 | c.43C>T | p.Arg15Trp | missense_variant | 3/43 | 1 | A2 | ||
MYO18B | ENST00000539302.5 | c.43C>T | p.Arg15Trp | missense_variant, NMD_transcript_variant | 2/42 | 1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000284 AC: 7AN: 246392Hom.: 0 AF XY: 0.0000299 AC XY: 4AN XY: 133822
GnomAD4 exome AF: 0.00000893 AC: 13AN: 1455686Hom.: 0 Cov.: 31 AF XY: 0.00000830 AC XY: 6AN XY: 723278
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152274Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74444
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 12, 2022 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 15 of the MYO18B protein (p.Arg15Trp). This variant is present in population databases (rs372043469, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYO18B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1383468). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at