2-210556736-G-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_001875.5(CPS1):c.3G>T(p.Met1?) variant causes a start lost change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (no stars).
Frequency
Genomes: not found (cov: 32)
Consequence
CPS1
NM_001875.5 start_lost
NM_001875.5 start_lost
Scores
8
5
3
Clinical Significance
Conservation
PhyloP100: 5.92
Genes affected
CPS1 (HGNC:2323): (carbamoyl-phosphate synthase 1) The mitochondrial enzyme encoded by this gene catalyzes synthesis of carbamoyl phosphate from ammonia and bicarbonate. This reaction is the first committed step of the urea cycle, which is important in the removal of excess urea from cells. The encoded protein may also represent a core mitochondrial nucleoid protein. Three transcript variants encoding different isoforms have been found for this gene. The shortest isoform may not be localized to the mitochondrion. Mutations in this gene have been associated with carbamoyl phosphate synthetase deficiency, susceptibility to persistent pulmonary hypertension, and susceptibility to venoocclusive disease after bone marrow transplantation.[provided by RefSeq, May 2010]
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ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Start lost variant, next in-frame start position is after 9 pathogenic variants. Next in-frame start position is after 56 codons. Genomic position: 210573337. Lost 0.037 part of the original CDS.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 2-210556736-G-T is Pathogenic according to our data. Variant chr2-210556736-G-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 554067.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CPS1 | NM_001875.5 | c.3G>T | p.Met1? | start_lost | Exon 1 of 38 | ENST00000233072.10 | NP_001866.2 |
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Congenital hyperammonemia, type I Pathogenic:1
Sep 26, 2017
Counsyl
Significance:Likely pathogenic
Review Status:no assertion criteria provided
Collection Method:clinical testing
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;T;T;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D
MetaSVM
Pathogenic
D
PhyloP100
PROVEAN
Benign
N;N;N;N;N;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D;D;.
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
0.85
.;.;.;.;P;.
Vest4
0.69, 0.85, 0.88
MutPred
Gain of catalytic residue at M1 (P = 0.0626);Gain of catalytic residue at M1 (P = 0.0626);.;.;Gain of catalytic residue at M1 (P = 0.0626);Gain of catalytic residue at M1 (P = 0.0626);
MVP
MPC
0.86
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
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