2-210600632-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The ENST00000233072.10(CPS1):c.1627G>A(p.Ala543Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000577 in 1,612,244 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

CPS1
ENST00000233072.10 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 4.45

Publications

1 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

CPS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 2-210600632-G-A is Benign according to our data. Variant chr2-210600632-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 576447.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000233072.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CPS1	NM_001875.5	MANE Select	c.1627G>A	p.Ala543Thr	missense	Exon 15 of 38	NP_001866.2
CPS1	NM_001369256.1		c.1660G>A	p.Ala554Thr	missense	Exon 16 of 39	NP_001356185.1
CPS1	NM_001122633.3		c.1627G>A	p.Ala543Thr	missense	Exon 16 of 39	NP_001116105.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
CPS1	ENST00000233072.10	TSL:1 MANE Select	c.1627G>A	p.Ala543Thr	missense	Exon 15 of 38	ENSP00000233072.5
CPS1	ENST00000430249.7	TSL:1	c.1645G>A	p.Ala549Thr	missense	Exon 16 of 39	ENSP00000402608.2
CPS1	ENST00000451903.3	TSL:1	c.274G>A	p.Ala92Thr	missense	Exon 5 of 28	ENSP00000406136.2

Frequencies

GnomAD3 genomes

AF:

0.0000593

AC:

AN:

151826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000108

AC:

AN:

250726

AF XY:

0.0000886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.0000575

AC:

AN:

1460300

Hom.:

Cov.:

AF XY:

0.0000564

AC XY:

AN XY:

726502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33360

American (AMR)

AF:

0.000314

AC:

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39636

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000567

AC:

AN:

1110986

Other (OTH)

AF:

0.0000829

AC:

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151944

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41520

American (AMR)

AF:

0.000197

AC:

AN:

15228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5110

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67872

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.0000869

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000115

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions as Germline

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital hyperammonemia, type I (2)

Pulmonary hypertension, neonatal, susceptibility to;C4082171:Congenital hyperammonemia, type I (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Uncertain

-0.030

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.14

Eigen

Benign

-0.029

Eigen_PC

Benign

0.054

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.065

MetaRNN

Uncertain

0.66

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

0.78

PhyloP100

4.5

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.78

REVEL

Uncertain

0.55

Sift

Benign

0.83

Sift4G

Benign

0.92

Polyphen

0.56

Vest4

0.68

MVP

0.90

MPC

0.36

ClinPred

0.084

GERP RS

4.2

Varity_R

0.50

gMVP

0.86

Mutation Taster

=26/74

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over