8-9141575-A-C

Position:

• chr8-9141575-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024607.4(PPP1R3B):​c.77T>G​(p.Ile26Ser) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R3B NM_024607.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.810

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 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=0.056791127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3B	NM_024607.4	c.77T>G	p.Ile26Ser	missense_variant	2/2	ENST00000310455.4	NP_078883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R3B	ENST00000310455.4	c.77T>G	p.Ile26Ser	missense_variant	2/2	1	NM_024607.4	ENSP00000308318.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.00000378

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

Jul 25, 2023

The c.77T>G (p.I26S) alteration is located in exon 2 (coding exon 1) of the PPP1R3B gene. This alteration results from a T to G substitution at nucleotide position 77, causing the isoleucine (I) at amino acid position 26 to be replaced by a serine (S). 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	0.15
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.043	T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.54	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.23	N;N
REVEL	Benign	0.031
Sift	Benign	0.53	T;T
Sift4G	Benign	0.77	T;T
Polyphen		0.047	B;B
Vest4		0.17
MutPred		0.43		Gain of relative solvent accessibility (P = 0.005);Gain of relative solvent accessibility (P = 0.005);
MVP		0.41
MPC		0.056
ClinPred		0.10	T
GERP RS		3.4
Varity_R		0.080
gMVP		0.28

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

LitVar

Other links and lift over

dbSNP: rs1384851260; hg19: chr8-8999085;