rs764894986
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_015164.4(PLEKHM2):c.461A>T(p.Asp154Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000083 in 1,325,524 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. D154H) has been classified as Uncertain significance.
Frequency
Consequence
NM_015164.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHM2 | NM_015164.4 | c.461A>T | p.Asp154Val | missense_variant | 5/20 | ENST00000375799.8 | |
PLEKHM2 | NM_001410755.1 | c.461A>T | p.Asp154Val | missense_variant | 5/19 | ||
PLEKHM2 | XM_017000757.1 | c.500A>T | p.Asp167Val | missense_variant | 5/20 | ||
PLEKHM2 | XM_017000758.1 | c.500A>T | p.Asp167Val | missense_variant | 5/19 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHM2 | ENST00000375799.8 | c.461A>T | p.Asp154Val | missense_variant | 5/20 | 1 | NM_015164.4 | P2 | |
PLEKHM2 | ENST00000375793.2 | c.461A>T | p.Asp154Val | missense_variant | 5/19 | 5 | A2 | ||
PLEKHM2 | ENST00000642363.1 | c.461A>T | p.Asp154Val | missense_variant | 5/21 | A2 | |||
PLEKHM2 | ENST00000462455.1 | n.369A>T | non_coding_transcript_exon_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000523 AC: 7AN: 133738Hom.: 0 Cov.: 30
GnomAD4 exome AF: 0.00000336 AC: 4AN: 1191786Hom.: 0 Cov.: 30 AF XY: 0.00000341 AC XY: 2AN XY: 586644
GnomAD4 genome ? AF: 0.0000523 AC: 7AN: 133738Hom.: 0 Cov.: 30 AF XY: 0.0000784 AC XY: 5AN XY: 63812
ClinVar
Submissions by phenotype
Dilated Cardiomyopathy, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 154 of the PLEKHM2 protein (p.Asp154Val). This variant is present in population databases (rs764894986, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with PLEKHM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 478100). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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