chrX-38369882-G-C
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000531.6(OTC):c.298+5G>C variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000432 in 1,152,072 control chromosomes in the GnomAD database, including 1 homozygotes. There are 160 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000531.6 splice_donor_5th_base, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTC | NM_000531.6 | c.298+5G>C | splice_donor_5th_base_variant, intron_variant | ENST00000039007.5 | |||
OTC | NM_001407092.1 | c.298+5G>C | splice_donor_5th_base_variant, intron_variant | ||||
OTC | XM_017029556.2 | c.298+5G>C | splice_donor_5th_base_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | c.298+5G>C | splice_donor_5th_base_variant, intron_variant | 1 | NM_000531.6 | P1 | |||
OTC | ENST00000643344.1 | c.298+5G>C | splice_donor_5th_base_variant, intron_variant, NMD_transcript_variant | ||||||
OTC | ENST00000488812.1 | n.353+42G>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.000677 AC: 76AN: 112191Hom.: 1 Cov.: 23 AF XY: 0.000582 AC XY: 20AN XY: 34343
GnomAD3 exomes AF: 0.00162 AC: 296AN: 183053Hom.: 0 AF XY: 0.00145 AC XY: 98AN XY: 67525
GnomAD4 exome AF: 0.000406 AC: 422AN: 1039832Hom.: 0 Cov.: 22 AF XY: 0.000443 AC XY: 139AN XY: 313636
GnomAD4 genome AF: 0.000677 AC: 76AN: 112240Hom.: 1 Cov.: 23 AF XY: 0.000610 AC XY: 21AN XY: 34402
ClinVar
Submissions by phenotype
Ornithine carbamoyltransferase deficiency Uncertain:1Benign:4
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Feb 27, 2018 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Apr 03, 2020 | - - |
Uncertain significance, no assertion criteria provided | curation | SingHealth Duke-NUS Institute of Precision Medicine | Jun 07, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 28, 2015 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 25, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | GenMed Metabolism Lab | - | - - |
Inborn genetic diseases Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2016 | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
OTC-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 21, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at