8-9141509-C-G

Variant names:

• chr8-9141509-C-G
• NM_024607.4:c.143G>C

Variant summary

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

The NM_024607.4(PPP1R3B):​c.143G>C​(p.Gly48Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G48E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R3B NM_024607.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

Genes affected

PPP1R3B (HGNC:14942): (protein phosphatase 1 regulatory subunit 3B) This gene encodes the catalytic subunit of the serine/theonine phosphatase, protein phosphatase-1. The encoded protein is expressed in liver and skeletal muscle tissue and may be involved in regulating glycogen synthesis in these tissues. This gene may be a involved in type 2 diabetes and maturity-onset diabetes of the young. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Jan 2011]

ENSG00000254340 (HGNC:):

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=0.27082568).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3B	NM_024607.4	c.143G>C	p.Gly48Ala	missense_variant	Exon 2 of 2	ENST00000310455.4	NP_078883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R3B	ENST00000310455.4	c.143G>C	p.Gly48Ala	missense_variant	Exon 2 of 2	1	NM_024607.4	ENSP00000308318.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.065	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.31
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.61	N;N
REVEL	Benign	0.047
Sift	Benign	0.35	T;T
Sift4G	Benign	0.57	T;T
Polyphen		0.32	B;B
Vest4		0.16
MutPred		0.11		Loss of glycosylation at S47 (P = 0.064);Loss of glycosylation at S47 (P = 0.064);
MVP		0.41
MPC		0.051
ClinPred		0.20	T
GERP RS		5.8
Varity_R		0.14
gMVP		0.33

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: chr8-8999019;