chrX-38352706-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4BP6_Moderate
The NM_000531.6(OTC):c.10A>G(p.Asn4Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000025 in 1,201,898 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 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 0.0000089 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )
Consequence
OTC
NM_000531.6 missense
NM_000531.6 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 1.53
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 Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.2999106).
BP6
?
Variant X-38352706-A-G is Benign according to our data. Variant chrX-38352706-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2092888.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTC | NM_000531.6 | c.10A>G | p.Asn4Asp | missense_variant | 1/10 | ENST00000039007.5 | |
OTC | NM_001407092.1 | c.10A>G | p.Asn4Asp | missense_variant | 3/12 | ||
OTC | XM_017029556.2 | c.10A>G | p.Asn4Asp | missense_variant | 1/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | c.10A>G | p.Asn4Asp | missense_variant | 1/10 | 1 | NM_000531.6 | P1 | |
OTC | ENST00000488812.1 | n.102A>G | non_coding_transcript_exon_variant | 1/6 | 5 | ||||
OTC | ENST00000643344.1 | c.10A>G | p.Asn4Asp | missense_variant, NMD_transcript_variant | 1/11 |
Frequencies
GnomAD3 genomes ? AF: 0.00000891 AC: 1AN: 112243Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0AN XY: 34395
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GnomAD3 exomes AF: 0.00000546 AC: 1AN: 183262Hom.: 0 AF XY: 0.0000148 AC XY: 1AN XY: 67752
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GnomAD4 exome AF: 0.00000184 AC: 2AN: 1089655Hom.: 0 Cov.: 27 AF XY: 0.00000281 AC XY: 1AN XY: 355515
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Ornithine carbamoyltransferase deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of MoRF binding (P = 0.0452);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
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