rs373347042

Variant summary

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

The NM_001166222.2(CARNS1):​c.287C>A​(p.Ala96Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000766 in 1,305,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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: not found (cov: 33)
Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

CARNS1
NM_001166222.2 missense

Scores

3
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.424
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]

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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=0.16542938).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CARNS1NM_001166222.2 linkc.287C>A p.Ala96Glu missense_variant Exon 4 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.287C>A p.Ala96Glu missense_variant Exon 4 of 10 NM_001166222.2 ENSP00000510668.1 A5YM72-5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.66e-7
AC:
1
AN:
1305054
Hom.:
0
Cov.:
31
AF XY:
0.00000157
AC XY:
1
AN XY:
636536
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000480
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
19
DANN
Uncertain
0.98
Eigen
Benign
-0.13
Eigen_PC
Benign
-0.047
FATHMM_MKL
Benign
0.28
N
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.0087
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.4
N;N
REVEL
Benign
0.033
Sift
Uncertain
0.022
D;D
Sift4G
Benign
0.071
T;T
Vest4
0.46
MVP
0.33
MPC
0.34
ClinPred
0.51
D
GERP RS
3.1
gMVP
0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-67185914; API