rs141050112

Variant names:

• chr2-28752151-C-G
• NM_002709.3:c.27C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-28752151-C-G
• chr2-28752151-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_002709.3(PPP1CB):​c.27C>G​(p.Asp9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,396,750 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: 30)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PPP1CB NM_002709.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

Genes affected

PPP1CB (HGNC:9282): (protein phosphatase 1 catalytic subunit beta) The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). 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. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2008]

ACMG classification

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=0.40261278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CB	NM_002709.3	c.27C>G	p.Asp9Glu	missense_variant	Exon 1 of 8	ENST00000395366.3	NP_002700.1
PPP1CB	NM_206876.2	c.27C>G	p.Asp9Glu	missense_variant	Exon 2 of 9		NP_996759.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1CB	ENST00000395366.3	c.27C>G	p.Asp9Glu	missense_variant	Exon 1 of 8	1	NM_002709.3	ENSP00000378769.2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396750 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 688926

Gnomad4 AFR exome AF: 0.0000321

Gnomad4 AMR exome AF: 0.00

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.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	.;T;D;D;D
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.20	N
LIST_S2	Uncertain	0.90	D;D;D;.;.
M_CAP	Uncertain	0.20	D
MetaRNN	Benign	0.40	T;T;T;T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Pathogenic	3.3	.;.;M;M;M
PrimateAI	Pathogenic	0.93	D
PROVEAN	Uncertain	-2.7	D;D;N;N;N
REVEL	Benign	0.22
Sift	Uncertain	0.022	D;D;D;D;D
Sift4G	Uncertain	0.054	T;T;T;T;T
Polyphen		0.0040	.;.;B;B;B
Vest4		0.18, 0.18, 0.17
MutPred		0.60		Gain of disorder (P = 0.1802);Gain of disorder (P = 0.1802);Gain of disorder (P = 0.1802);Gain of disorder (P = 0.1802);Gain of disorder (P = 0.1802);
MVP		0.72
MPC		2.8
ClinPred		0.95	D
GERP RS		0.86
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		3.9
Varity_R		0.24
gMVP		0.92

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: chr2-28975017;