rs118003416
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_181882.3(PRX):c.1964C>T(p.Pro655Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000651 in 1,613,766 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRX | NM_181882.3 | c.1964C>T | p.Pro655Leu | missense_variant | Exon 7 of 7 | ENST00000324001.8 | NP_870998.2 | |
PRX | NM_001411127.1 | c.2249C>T | p.Pro750Leu | missense_variant | Exon 7 of 7 | NP_001398056.1 | ||
PRX | XM_017027047.2 | c.1862C>T | p.Pro621Leu | missense_variant | Exon 4 of 4 | XP_016882536.1 | ||
PRX | NM_020956.2 | c.*2169C>T | 3_prime_UTR_variant | Exon 6 of 6 | NP_066007.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000790 AC: 120AN: 151836Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.00204 AC: 513AN: 251004Hom.: 2 AF XY: 0.00197 AC XY: 267AN XY: 135834
GnomAD4 exome AF: 0.000637 AC: 931AN: 1461814Hom.: 6 Cov.: 37 AF XY: 0.000594 AC XY: 432AN XY: 727216
GnomAD4 genome AF: 0.000790 AC: 120AN: 151952Hom.: 3 Cov.: 33 AF XY: 0.000727 AC XY: 54AN XY: 74260
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease Benign:1
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Dejerine-Sottas disease;C3540453:Charcot-Marie-Tooth disease type 4F Benign:1
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Charcot-Marie-Tooth disease type 4F Benign:1
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
This variant is associated with the following publications: (PMID: 22730194, 25614874) -
Charcot-Marie-Tooth disease type 4 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at