rs72558451
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PM5
The NM_000531.6(OTC):c.808C>A(p.Gln270Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q270P) has been classified as Pathogenic.
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.000016 ( 0 hom. 4 hem. )
Failed GnomAD Quality Control
Consequence
OTC
NM_000531.6 missense
NM_000531.6 missense
Scores
6
9
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.48
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_pathogenic. Variant got 6 ACMG points.
PM1
?
In a hotspot region, there are 9 aminoacids with missense pathogenic changes in the window of +-8 aminoacids around while only 0 benign, 6 uncertain in NM_000531.6
PM2
?
Very rare variant in population databases, with high coverage;
PM5
?
Other missense variant is known to change same aminoacid residue: Variant chrX-38408967-A-C is described in ClinVar as [Pathogenic]. Clinvar id is 97336.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTC | NM_000531.6 | c.808C>A | p.Gln270Lys | missense_variant | 8/10 | ENST00000039007.5 | |
OTC | NM_001407092.1 | c.808C>A | p.Gln270Lys | missense_variant | 10/12 | ||
OTC | XM_017029556.2 | c.808C>A | p.Gln270Lys | missense_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | c.808C>A | p.Gln270Lys | missense_variant | 8/10 | 1 | NM_000531.6 | P1 | |
OTC | ENST00000643344.1 | c.*558C>A | 3_prime_UTR_variant, NMD_transcript_variant | 9/11 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000164 AC: 15AN: 915982Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 4AN XY: 295214
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
15
AN:
915982
Hom.:
Cov.:
31
AF XY:
AC XY:
4
AN XY:
295214
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 ASJ exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Pathogenic
D
MutationAssessor
Uncertain
M
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D
REVEL
Pathogenic
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MutPred
Gain of methylation at Q270 (P = 0.0124);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.