rs779799130
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_020631.6(PLEKHG5):c.1264C>T(p.Leu422Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000404 in 1,610,674 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L422L) has been classified as Likely benign.
Frequency
Consequence
NM_020631.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHG5 | NM_020631.6 | c.1264C>T | p.Leu422Phe | missense_variant | 12/21 | ENST00000377728.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHG5 | ENST00000377728.8 | c.1264C>T | p.Leu422Phe | missense_variant | 12/21 | 2 | NM_020631.6 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152180Hom.: 1 Cov.: 33
GnomAD3 exomes AF: 0.0000682 AC: 16AN: 234664Hom.: 0 AF XY: 0.0000854 AC XY: 11AN XY: 128838
GnomAD4 exome AF: 0.0000418 AC: 61AN: 1458376Hom.: 0 Cov.: 33 AF XY: 0.0000593 AC XY: 43AN XY: 725474
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152298Hom.: 1 Cov.: 33 AF XY: 0.0000537 AC XY: 4AN XY: 74468
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 12, 2024 | The c.1264C>T (p.L422F) alteration is located in exon 12 (coding exon 11) of the PLEKHG5 gene. This alteration results from a C to T substitution at nucleotide position 1264, causing the leucine (L) at amino acid position 422 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Neuronopathy, distal hereditary motor, autosomal recessive 4;C3809309:Charcot-Marie-Tooth disease recessive intermediate C Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces leucine with phenylalanine at codon 422 of the PLEKHG5 protein (p.Leu422Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs779799130, ExAC 0.05%). This variant has not been reported in the literature in individuals affected with PLEKHG5-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The phenylalanine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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