8-9141229-C-A

Variant names:

• chr8-9141229-C-A
• NM_024607.4:c.423G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024607.4(PPP1R3B):​c.423G>T​(p.Lys141Asn) 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 pathogenic 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: 0.106

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.81

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3B	NM_024607.4	c.423G>T	p.Lys141Asn	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.423G>T	p.Lys141Asn	missense_variant	Exon 2 of 2	1	NM_024607.4	ENSP00000308318.3
PPP1R3B	ENST00000519699.1	c.423G>T	p.Lys141Asn	missense_variant	Exon 2 of 2	2		ENSP00000428642.1
ENSG00000254340	ENST00000520017.1	n.-195C>A		upstream_gene_variant		3
ENSG00000254340	ENST00000666082.1	n.-198C>A		upstream_gene_variant

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

May 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.423G>T (p.K141N) 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 423, causing the lysine (K) at amino acid position 141 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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.073
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.084	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Uncertain	0.66	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.037	D;D
Polyphen		1.0	D;D
Vest4		0.69
MutPred		0.49		Loss of ubiquitination at K141 (P = 0.0233);Loss of ubiquitination at K141 (P = 0.0233);
MVP		0.82
MPC		0.31
ClinPred		0.99	D
GERP RS		-0.12
Varity_R		0.63
gMVP		0.68

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: chr8-8998739;