8-9141565-C-A

Position:

• chr8-9141565-C-A

Variant summary

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

The NM_024607.4(PPP1R3B):​c.87G>T​(p.Lys29Asn) 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. 14/21 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: 0.504

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1970272).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3B	NM_024607.4	c.87G>T	p.Lys29Asn	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.87G>T	p.Lys29Asn	missense_variant	2/2	1	NM_024607.4	ENSP00000308318.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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

Nov 30, 2022

The c.87G>T (p.K29N) alteration is located in exon 2 (coding exon 1) of the PPP1R3B gene. This alteration results from a G to T substitution at nucleotide position 87, causing the lysine (K) at amino acid position 29 to be replaced by an asparagine (N). 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	0.27
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.033	T;T
Eigen	Benign	0.014
Eigen_PC	Benign	-0.044
FATHMM_MKL	Uncertain	0.78	D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.20	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.17	N;N
REVEL	Benign	0.12
Sift	Benign	0.095	T;T
Sift4G	Benign	0.46	T;T
Polyphen		0.99	D;D
Vest4		0.10
MutPred		0.28		Loss of methylation at K29 (P = 0.0127);Loss of methylation at K29 (P = 0.0127);
MVP		0.69
MPC		0.12
ClinPred		0.57	D
GERP RS		3.9
Varity_R		0.11
gMVP		0.31

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: chr8-8999075;