rs139586219
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_181882.3(PRX):c.1625G>A(p.Arg542Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000577 in 1,611,704 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R542W) has been classified as Likely benign.
Frequency
Consequence
NM_181882.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRX | NM_181882.3 | c.1625G>A | p.Arg542Gln | missense_variant | 7/7 | ENST00000324001.8 | |
PRX | NM_001411127.1 | c.1910G>A | p.Arg637Gln | missense_variant | 7/7 | ||
PRX | XM_017027047.2 | c.1523G>A | p.Arg508Gln | missense_variant | 4/4 | ||
PRX | NM_020956.2 | c.*1830G>A | 3_prime_UTR_variant | 6/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRX | ENST00000324001.8 | c.1625G>A | p.Arg542Gln | missense_variant | 7/7 | 1 | NM_181882.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000783 AC: 118AN: 150644Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.00108 AC: 270AN: 249672Hom.: 2 AF XY: 0.00114 AC XY: 154AN XY: 135260
GnomAD4 exome AF: 0.000556 AC: 812AN: 1460942Hom.: 7 Cov.: 37 AF XY: 0.000555 AC XY: 403AN XY: 726730
GnomAD4 genome ? AF: 0.000783 AC: 118AN: 150762Hom.: 3 Cov.: 33 AF XY: 0.000719 AC XY: 53AN XY: 73726
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Molecular Genetics Laboratory, London Health Sciences Centre | - | - - |
Dejerine-Sottas disease;C3540453:Charcot-Marie-Tooth disease type 4F Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 20, 2021 | - - |
Charcot-Marie-Tooth disease type 4F Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 30, 2018 | This variant is associated with the following publications: (PMID: 22730194) - |
Charcot-Marie-Tooth disease type 4 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at