chr2-210592937-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PM5

The NM_001875.5(CPS1):​c.1145C>G​(p.Pro382Arg) 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. P382L) has been classified as Likely pathogenic.

Frequency

Genomes: not found (cov: 32)

Consequence

CPS1
NM_001875.5 missense

Scores

9
9
1

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.92

Publications

0 publications found
Variant links:
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]
CPS1 Gene-Disease associations (from GenCC):
  • carbamoyl phosphate synthetase I deficiency disease
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr2-210592937-C-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 550641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CPS1NM_001875.5 linkc.1145C>G p.Pro382Arg missense_variant Exon 11 of 38 ENST00000233072.10 NP_001866.2 P31327-1A0A024R454Q6PEK7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CPS1ENST00000233072.10 linkc.1145C>G p.Pro382Arg missense_variant Exon 11 of 38 1 NM_001875.5 ENSP00000233072.5 P31327-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.42
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.15
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.90
.;D;D
Eigen
Pathogenic
0.91
Eigen_PC
Pathogenic
0.88
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Uncertain
0.13
D
MetaRNN
Uncertain
0.73
D;D;D
MetaSVM
Pathogenic
0.93
D
MutationAssessor
Pathogenic
3.2
.;M;.
PhyloP100
5.9
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-4.8
D;D;.
REVEL
Pathogenic
0.70
Sift
Uncertain
0.011
D;D;.
Sift4G
Uncertain
0.024
D;D;D
Polyphen
0.98
.;D;.
Vest4
0.66
MutPred
0.54
.;Gain of solvent accessibility (P = 0.0216);Gain of solvent accessibility (P = 0.0216);
MVP
0.97
MPC
0.65
ClinPred
1.0
D
GERP RS
6.0
PromoterAI
-0.020
Neutral
Varity_R
0.62
gMVP
0.90
Mutation Taster
=38/62
disease causing

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs201407486; hg19: chr2-211457661; API