Variant chr2-182117233-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001080545.3(PPP1R1C):c.268G>A(p.Glu90Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000311 in 1,560,374 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 1 hom. )

Consequence

PPP1R1C
NM_001080545.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.76

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.019280463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R1C	NM_001080545.3 linkuse as main transcript	c.268G>A	p.Glu90Lys	missense_variant	5/5	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.268G>A	p.Glu90Lys	missense_variant	5/5		NM_001080545.3	ENSP00000507052.1		Q8WVI7-1

Frequencies

GnomAD3 genomes

AF:

0.000296

AC:

AN:

152164

Hom.:

Cov.:

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:

0.000662

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000293

AC:

AN:

173848

Hom.:

AF XY:

0.000295

AC XY:

AN XY:

91666

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000384

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000564

Gnomad NFE exome

AF:

0.000669

Gnomad OTH exome

AF:

0.000210

GnomAD4 exome

AF:

0.000313

AC:

441

AN:

1408094

Hom.:

Cov.:

AF XY:

0.000335

AC XY:

233

AN XY:

695386

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000109

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000119

Gnomad4 NFE exome

AF:

0.000383

Gnomad4 OTH exome

AF:

0.000273

GnomAD4 genome

AF:

0.000296

AC:

AN:

152280

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74458

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:

0.000662

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000664

Hom.:

Bravo

AF:

0.000276

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000611

AC:

ExAC

AF:

0.000266

AC:

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

Oct 06, 2021

The c.268G>A (p.E90K) alteration is located in exon 5 (coding exon 5) of the PPP1R1C gene. This alteration results from a G to A substitution at nucleotide position 268, causing the glutamic acid (E) at amino acid position 90 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

Benign

0.099

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.015

T;.;T

Eigen

Benign

0.047

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.76

.;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.019

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

N;.;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.76

N;N;N

REVEL

Benign

0.11

Sift

Benign

0.42

T;T;T

Sift4G

Benign

0.70

T;T;T

Polyphen

0.32

B;P;B

Vest4

0.20

MVP

0.061

MPC

0.36

ClinPred

0.041

GERP RS

5.8

Varity_R

0.21

gMVP

0.088

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over