rs375524303
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_000531.6(OTC):c.1005+11A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000063 in 1,207,023 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000045 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.000065 ( 0 hom. 23 hem. )
Consequence
OTC
NM_000531.6 intron
NM_000531.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.461
Genes affected
OTC (HGNC:8512): (ornithine transcarbamylase) This nuclear gene encodes a mitochondrial matrix enzyme. The encoded protein is involved in the urea cycle which functions to detoxify ammonia into urea for excretion. Mutations in this enzyme lead to ornithine transcarbamylase deficiency, which causes hyperammonemia. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant X-38412010-A-T is Benign according to our data. Variant chrX-38412010-A-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 523373.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.
BS2
?
High Hemizygotes in GnomAdExome4 at 23 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTC | NM_000531.6 | c.1005+11A>T | intron_variant | ENST00000039007.5 | |||
OTC | NM_001407092.1 | c.1005+11A>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | c.1005+11A>T | intron_variant | 1 | NM_000531.6 | P1 | |||
OTC | ENST00000643344.1 | c.*755+11A>T | intron_variant, NMD_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000445 AC: 5AN: 112279Hom.: 0 Cov.: 23 AF XY: 0.0000290 AC XY: 1AN XY: 34427
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GnomAD3 exomes AF: 0.0000983 AC: 18AN: 183143Hom.: 0 AF XY: 0.0000887 AC XY: 6AN XY: 67659
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GnomAD4 exome AF: 0.0000649 AC: 71AN: 1094744Hom.: 0 Cov.: 29 AF XY: 0.0000639 AC XY: 23AN XY: 360214
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GnomAD4 genome ? AF: 0.0000445 AC: 5AN: 112279Hom.: 0 Cov.: 23 AF XY: 0.0000290 AC XY: 1AN XY: 34427
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Ornithine carbamoyltransferase deficiency Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jul 03, 2019 | This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: BS2. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Global developmental delay;C5574662:Hyperammonemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2017 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at