NM_001369496.1:c.187C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001369496.1(TBC1D10C):ā€‹c.187C>Gā€‹(p.Arg63Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 1,399,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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 š‘“: 0.0000021 ( 0 hom. )

Consequence

TBC1D10C
NM_001369496.1 missense

Scores

4
9
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0200
Variant links:
Genes affected
TBC1D10C (HGNC:24702): (TBC1 domain family member 10C) The protein encoded by this gene has an N-terminal Rab-GTPase domain and a binding site at the C-terminus for calcineurin, and is an inhibitor of both the Ras signaling pathway and calcineurin, a phosphatase regulated by calcium and calmodulin. Genes encoding similar proteins are located on chromosomes 16 and 22. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2013]
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.35067788).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TBC1D10CNM_001369496.1 linkc.187C>G p.Arg63Gly missense_variant Exon 2 of 9 ENST00000542590.2 NP_001356425.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TBC1D10CENST00000542590.2 linkc.187C>G p.Arg63Gly missense_variant Exon 2 of 9 1 NM_001369496.1 ENSP00000443654.1 Q8IV04-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000214
AC:
3
AN:
1399090
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
690058
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000839
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
AlphaMissense
Pathogenic
0.83
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.45
.;.;T
Eigen
Uncertain
0.24
Eigen_PC
Benign
0.14
FATHMM_MKL
Benign
0.43
N
LIST_S2
Uncertain
0.94
.;D;D
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.35
T;T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Pathogenic
3.1
M;M;M
PrimateAI
Uncertain
0.69
T
PROVEAN
Pathogenic
-6.7
D;D;D
REVEL
Uncertain
0.30
Sift
Uncertain
0.0010
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.85
.;.;P
Vest4
0.58
MutPred
0.56
Loss of catalytic residue at R63 (P = 0.0206);Loss of catalytic residue at R63 (P = 0.0206);Loss of catalytic residue at R63 (P = 0.0206);
MVP
0.58
MPC
0.88
ClinPred
0.98
D
GERP RS
3.1
Varity_R
0.79
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs147100387; hg19: chr11-67172590; API