1-15733845-T-C
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_015164.4(PLEKHM2):c.2971T>C(p.Phe991Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,612,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_015164.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHM2 | NM_015164.4 | c.2971T>C | p.Phe991Leu | missense_variant | 20/20 | ENST00000375799.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHM2 | ENST00000375799.8 | c.2971T>C | p.Phe991Leu | missense_variant | 20/20 | 1 | NM_015164.4 | P2 | |
ENST00000453804.1 | n.37-1284A>G | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152072Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248788Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135126
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1460784Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 726702
GnomAD4 genome AF: 0.000171 AC: 26AN: 152190Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74380
ClinVar
Submissions by phenotype
Dilated Cardiomyopathy, Recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2023 | This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 991 of the PLEKHM2 protein (p.Phe991Leu). This variant is present in population databases (rs201091991, gnomAD 0.05%). 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: 544340). 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 tolerated. 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