rs774158852

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001166222.2(CARNS1):ā€‹c.727C>Gā€‹(p.Arg243Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000254 in 1,573,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000021 ( 0 hom. )

Consequence

CARNS1
NM_001166222.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.119
Variant links:
Genes affected
CARNS1 (HGNC:29268): (carnosine synthase 1) CARNS1 (EC 6.3.2.11), a member of the ATP-grasp family of ATPases, catalyzes the formation of carnosine (beta-alanyl-L-histidine) and homocarnosine (gamma-aminobutyryl-L-histidine), which are found mainly in skeletal muscle and the central nervous system, respectively (Drozak et al., 2010 [PubMed 20097752]).[supplied by OMIM, Apr 2010]
PPP1CA (HGNC:9281): (protein phosphatase 1 catalytic subunit alpha) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). This broadly expressed gene encodes the alpha subunit of the PP1 complex that associates with over 200 regulatory proteins to form holoenzymes which dephosphorylate their biological targets with high specificity. PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies suggest that PP1 is an important regulator of cardiac function and that PP1 deregulation is implicated in diabetes and multiple types of cancer. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2020]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07366413).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARNS1NM_001166222.2 linkc.727C>G p.Arg243Gly missense_variant Exon 5 of 10 ENST00000687366.1 NP_001159694.1 A5YM72-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CARNS1ENST00000687366.1 linkc.727C>G p.Arg243Gly missense_variant Exon 5 of 10 NM_001166222.2 ENSP00000510668.1 A5YM72-5

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152080
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000211
AC:
3
AN:
1420934
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
701932
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000275
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152080
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
7.4
DANN
Benign
0.90
DEOGEN2
Benign
0.0041
.;T;.
Eigen
Benign
-0.99
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.73
T;T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.074
T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
.;L;.
PrimateAI
Benign
0.32
T
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.086
Sift
Uncertain
0.018
D;D;D
Sift4G
Benign
0.11
T;T;T
Polyphen
0.0060
.;B;.
Vest4
0.38
MutPred
0.35
.;Loss of methylation at R120 (P = 0.0204);.;
MVP
0.13
MPC
0.15
ClinPred
0.061
T
GERP RS
-0.00031
Varity_R
0.12
gMVP
0.41

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs774158852; hg19: chr11-67186589; API