8-9141509-C-G

Variant names:

• chr8-9141509-C-G
• rs3748140
• NM_024607.4:c.143G>C

Variant summary

Our verdict is Uncertain significance. The variant received 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. 16/22 in silico tools predict 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: 32)
• Consequence: PPP1R3B NM_024607.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51
• Publications: 0 publications found

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:58434):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27082568).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024607.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3B	NM_024607.4	MANE Select	c.143G>C	p.Gly48Ala	missense	Exon 2 of 2	NP_078883.2	Q86XI6
	PPP1R3B	NM_001201329.2		c.143G>C	p.Gly48Ala	missense	Exon 2 of 2	NP_001188258.1	Q86XI6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3B	ENST00000310455.4	TSL:1 MANE Select	c.143G>C	p.Gly48Ala	missense	Exon 2 of 2	ENSP00000308318.3	Q86XI6
	PPP1R3B	ENST00000519699.1	TSL:2	c.143G>C	p.Gly48Ala	missense	Exon 2 of 2	ENSP00000428642.1	Q86XI6
	ENSG00000254340	ENST00000520017.1	TSL:3	n.86C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
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
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		1.5
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.047
Sift	Benign	0.35	T
Sift4G	Benign	0.57	T
Polyphen		0.32	B
Vest4		0.16
MutPred		0.11		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
Mutation Taster		=80/20	polymorphism

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

Other links and lift over

dbSNP: rs3748140; hg19: chr8-8999019;