chr1-6473042-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_020631.6(PLEKHG5):c.928G>A(p.Asp310Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,614,058 control chromosomes in the GnomAD database, including 12 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_020631.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PLEKHG5 | NM_020631.6 | c.928G>A | p.Asp310Asn | missense_variant | 9/21 | ENST00000377728.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PLEKHG5 | ENST00000377728.8 | c.928G>A | p.Asp310Asn | missense_variant | 9/21 | 2 | NM_020631.6 | P2 |
Frequencies
GnomAD3 genomes AF: 0.00235 AC: 358AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00257 AC: 644AN: 250440Hom.: 1 AF XY: 0.00243 AC XY: 329AN XY: 135416
GnomAD4 exome AF: 0.00288 AC: 4207AN: 1461726Hom.: 12 Cov.: 34 AF XY: 0.00272 AC XY: 1976AN XY: 727144
GnomAD4 genome AF: 0.00236 AC: 359AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.00252 AC XY: 188AN XY: 74484
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Sep 02, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | The PLEKHG5 c.928G>A; p.Asp310Asn variant (rs61730399), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 297961). This variant is found in the general population with an overall allele frequency of 0.25% (702/281,830 alleles, including 1 homozygote) in the Genome Aggregation Database. The aspartic acid at codon 310 is weakly conserved, and computational analyses predict that this variant is neutral (REVEL: 0.075). However, due to limited information, the clinical significance of the p.Asp310Asn variant is uncertain at this time. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 20, 2021 | - - |
Neuronopathy, distal hereditary motor, autosomal recessive 4 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Neuronopathy, distal hereditary motor, autosomal recessive 4;C3809309:Charcot-Marie-Tooth disease recessive intermediate C Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
PLEKHG5-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 26, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at