19-40396791-GTACCTCTGGAAGCCGCACCTCCGGCACAGCCATCTCTGGCACCTTTGGGAGTTTCATCTCTGACACTTTGGGCAGCTC-GTACCTCTGGAAGCCGCACCTCCGGCACAGCCATCTCTGGCACCTTTGGGAGTTTCATCTCTGACACTTTGGGCAGCTCTACCTCTGGAAGCCGCACCTCCGGCACAGCCATCTCTGGCACCTTTGGGAGTTTCATCTCTGACACTTTGGGCAGCTC
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_181882.3(PRX):c.1483_1560dupGAGCTGCCCAAAGTGTCAGAGATGAAACTCCCAAAGGTGCCAGAGATGGCTGTGCCGGAGGTGCGGCTTCCAGAGGTA(p.Val520_Gln521insGluLeuProLysValSerGluMetLysLeuProLysValProGluMetAlaValProGluValArgLeuProGluVal) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_181882.3 conservative_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRX | NM_181882.3 | c.1483_1560dupGAGCTGCCCAAAGTGTCAGAGATGAAACTCCCAAAGGTGCCAGAGATGGCTGTGCCGGAGGTGCGGCTTCCAGAGGTA | p.Val520_Gln521insGluLeuProLysValSerGluMetLysLeuProLysValProGluMetAlaValProGluValArgLeuProGluVal | conservative_inframe_insertion | Exon 7 of 7 | ENST00000324001.8 | NP_870998.2 | |
PRX | NM_001411127.1 | c.1768_1845dupGAGCTGCCCAAAGTGTCAGAGATGAAACTCCCAAAGGTGCCAGAGATGGCTGTGCCGGAGGTGCGGCTTCCAGAGGTA | p.Val615_Gln616insGluLeuProLysValSerGluMetLysLeuProLysValProGluMetAlaValProGluValArgLeuProGluVal | conservative_inframe_insertion | Exon 7 of 7 | NP_001398056.1 | ||
PRX | XM_017027047.2 | c.1381_1458dupGAGCTGCCCAAAGTGTCAGAGATGAAACTCCCAAAGGTGCCAGAGATGGCTGTGCCGGAGGTGCGGCTTCCAGAGGTA | p.Val486_Gln487insGluLeuProLysValSerGluMetLysLeuProLysValProGluMetAlaValProGluValArgLeuProGluVal | conservative_inframe_insertion | Exon 4 of 4 | XP_016882536.1 | ||
PRX | NM_020956.2 | c.*1688_*1765dupGAGCTGCCCAAAGTGTCAGAGATGAAACTCCCAAAGGTGCCAGAGATGGCTGTGCCGGAGGTGCGGCTTCCAGAGGTA | 3_prime_UTR_variant | Exon 6 of 6 | NP_066007.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRX | ENST00000324001.8 | c.1483_1560dupGAGCTGCCCAAAGTGTCAGAGATGAAACTCCCAAAGGTGCCAGAGATGGCTGTGCCGGAGGTGCGGCTTCCAGAGGTA | p.Val520_Gln521insGluLeuProLysValSerGluMetLysLeuProLysValProGluMetAlaValProGluValArgLeuProGluVal | conservative_inframe_insertion | Exon 7 of 7 | 1 | NM_181882.3 | ENSP00000326018.6 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 36
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 4 Uncertain:1
Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of this variant is currently unknown. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with PRX-related conditions. This variant is not present in population databases (ExAC no frequency). This variant, c.1483_1560dup, results in the insertion of 26 amino acid(s) to the PRX protein (p.Glu495_Val520dup), but otherwise preserves the integrity of the reading frame. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at