chrX-38381429-G-T
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM1PM2PM5PP3_StrongPP5
The NM_000531.6(OTC):c.386G>T(p.Arg129Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R129P) has been classified as Pathogenic.
Frequency
Consequence
NM_000531.6 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTC | NM_000531.6 | c.386G>T | p.Arg129Leu | missense_variant, splice_region_variant | 4/10 | ENST00000039007.5 | |
OTC | NM_001407092.1 | c.386G>T | p.Arg129Leu | missense_variant, splice_region_variant | 6/12 | ||
OTC | XM_017029556.2 | c.386G>T | p.Arg129Leu | missense_variant, splice_region_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | c.386G>T | p.Arg129Leu | missense_variant, splice_region_variant | 4/10 | 1 | NM_000531.6 | P1 | |
OTC | ENST00000488812.1 | n.423G>T | splice_region_variant, non_coding_transcript_exon_variant | 4/6 | 5 | ||||
OTC | ENST00000643344.1 | c.*136G>T | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 5/11 |
Frequencies
GnomAD3 genomes Cov.: 23
GnomAD4 exome Cov.: 23
GnomAD4 genome Cov.: 23
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | GenMed Metabolism Lab | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at