rs768780957
Variant names:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_000531.6(OTC):c.360G>A(p.Val120Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000159 in 1,198,156 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.000015 ( 0 hom. 4 hem. )
Consequence
OTC
NM_000531.6 synonymous
NM_000531.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.413
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 -15 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
Variant X-38381403-G-A is Benign according to our data. Variant chrX-38381403-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 529419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.413 with no splicing effect.
BS2
High Hemizygotes in GnomAdExome4 at 4 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTC | NM_000531.6 | c.360G>A | p.Val120Val | synonymous_variant | Exon 4 of 10 | ENST00000039007.5 | NP_000522.3 | |
OTC | NM_001407092.1 | c.360G>A | p.Val120Val | synonymous_variant | Exon 6 of 12 | NP_001394021.1 | ||
OTC | XM_017029556.2 | c.360G>A | p.Val120Val | synonymous_variant | Exon 4 of 9 | XP_016885045.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | c.360G>A | p.Val120Val | synonymous_variant | Exon 4 of 10 | 1 | NM_000531.6 | ENSP00000039007.4 | ||
ENSG00000250349 | ENST00000465127.1 | c.172-284718G>A | intron_variant | Intron 3 of 8 | 5 | ENSP00000417050.1 |
Frequencies
GnomAD3 genomes AF: 0.0000270 AC: 3AN: 111302Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33522
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GnomAD3 exomes AF: 0.0000273 AC: 5AN: 183132Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67622
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GnomAD4 exome AF: 0.0000147 AC: 16AN: 1086854Hom.: 0 Cov.: 27 AF XY: 0.0000113 AC XY: 4AN XY: 352938
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GnomAD4 genome AF: 0.0000270 AC: 3AN: 111302Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33522
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Ornithine carbamoyltransferase deficiency Benign:2
Apr 08, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Dec 01, 2023
All of Us Research Program, National Institutes of Health
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at