Variant 2-181987858-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001080545.3(PPP1R1C):c.101C>A(p.Thr34Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PPP1R1C
NM_001080545.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

Variant links:

Genes affected

PPP1R1C (HGNC:14940): (protein phosphatase 1 regulatory inhibitor subunit 1C) Protein phosphatase-1 (PP1) is a major serine/threonine phosphatase that regulates a variety of cellular functions. PP1 consists of a catalytic subunit (see PPP1CA; MIM 176875) and regulatory subunits that determine the subcellular localization of PP1 or regulate its function. PPP1R1C belongs to a group of PP1 inhibitory subunits that are themselves regulated by phosphorylation (Wang et al., 2008 [PubMed 18310074]).[supplied by OMIM, Feb 2010]

PPP1R1C links:

PPP1R1C (HGNC:):

PPP1R1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R1C	NM_001080545.3 linkuse as main transcript	c.101C>A	p.Thr34Lys	missense_variant	2/5	ENST00000682840.1	NP_001074014.1	Q8WVI7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R1C	ENST00000682840.1 linkuse as main transcript	c.101C>A	p.Thr34Lys	missense_variant	2/5		NM_001080545.3	ENSP00000507052.1		Q8WVI7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461158

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 04, 2022

The c.101C>A (p.T34K) alteration is located in exon 2 (coding exon 2) of the PPP1R1C gene. This alteration results from a C to A substitution at nucleotide position 101, causing the threonine (T) at amino acid position 34 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.98

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.26

T;.;T

Eigen

Pathogenic

0.89

Eigen_PC

Pathogenic

0.88

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

.;D;D

M_CAP

Benign

0.030

MetaRNN

Pathogenic

0.88

D;D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.7

M;.;M

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-6.0

D;D;D

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.95

MutPred

0.64

Loss of phosphorylation at T34 (P = 0.0136);.;Loss of phosphorylation at T34 (P = 0.0136);

MVP

0.62

MPC

1.1

ClinPred

0.99

GERP RS

6.2

Varity_R

0.89

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over