chr2-181987888-A-G

Position:

• chr2-181987888-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001080545.3(PPP1R1C):​c.131A>G​(p.His44Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: PPP1R1C NM_001080545.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.84

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 (HGNC:):

ACMG classification

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=0.1994882).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R1C	NM_001080545.3	c.131A>G	p.His44Arg	missense_variant	2/5	ENST00000682840.1	NP_001074014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R1C	ENST00000682840.1	c.131A>G	p.His44Arg	missense_variant	2/5		NM_001080545.3	ENSP00000507052.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.131A>G (p.H44R) alteration is located in exon 2 (coding exon 2) of the PPP1R1C gene. This alteration results from a A to G substitution at nucleotide position 131, causing the histidine (H) at amino acid position 44 to be replaced by an arginine (R). 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	0.13
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T;.;T
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.83	.;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.20	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.2	M;.;M
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.3	D;D;D
REVEL	Benign	0.091
Sift	Benign	0.075	T;T;T
Sift4G	Benign	0.45	T;T;T
Polyphen		0.38	B;D;B
Vest4		0.50
MutPred		0.30		Loss of catalytic residue at N45 (P = 0.1354);.;Loss of catalytic residue at N45 (P = 0.1354);
MVP		0.32
MPC		0.64
ClinPred		0.97	D
GERP RS		5.0
Varity_R		0.32
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr2-182852615;