chr8-9141509-C-T

Position:

• chr8-9141509-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024607.4(PPP1R3B):​c.143G>A​(p.Gly48Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,614,174 control chromosomes in the GnomAD database, including 1,225 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.026 (139 hom., cov: 32)
  • Exomes 𝑓: 0.020 (1086 hom.)
• 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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014359355).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3B	NM_024607.4	c.143G>A	p.Gly48Glu	missense_variant	2/2	ENST00000310455.4	NP_078883.2
LOC124901882	XR_007060810.1	n.91C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R3B	ENST00000310455.4	c.143G>A	p.Gly48Glu	missense_variant	2/2	1	NM_024607.4	ENSP00000308318	P1
	ENST00000666082.1	n.83C>T		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3890 AN: 152168 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.0411

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0137

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.0143

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0224

GnomAD3 exomes AF: 0.0311 AC: 7816 AN: 251446 Hom.: 353 AF XY: 0.0349 AC XY: 4738 AN XY: 135896

Gnomad AFR exome AF: 0.0418

Gnomad AMR exome AF: 0.0103

Gnomad ASJ exome AF: 0.00526

Gnomad EAS exome AF: 0.0626

Gnomad SAS exome AF: 0.129

Gnomad FIN exome AF: 0.0114

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.0231

GnomAD4 exome AF: 0.0204 AC: 29835 AN: 1461888 Hom.: 1086 Cov.: 35 AF XY: 0.0233 AC XY: 16940 AN XY: 727246

Gnomad4 AFR exome AF: 0.0434

Gnomad4 AMR exome AF: 0.0111

Gnomad4 ASJ exome AF: 0.00425

Gnomad4 EAS exome AF: 0.0741

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.0113

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.0262

GnomAD4 genome AF: 0.0256 AC: 3899 AN: 152286 Hom.: 139 Cov.: 32 AF XY: 0.0280 AC XY: 2087 AN XY: 74440

Gnomad4 AFR AF: 0.0410

Gnomad4 AMR AF: 0.0137

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.0711

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0143

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.0232

Alfa AF: 0.0144 Hom.: 61

Bravo AF: 0.0224

TwinsUK AF: 0.00971 AC: 36

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.0420 AC: 185

ESP6500EA AF: 0.0107 AC: 92

ExAC AF: 0.0334 AC: 4058

Asia WGS AF: 0.107 AC: 370 AN: 3478

EpiCase AF: 0.0105

EpiControl AF: 0.0133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.86
DEOGEN2	Benign	0.032	T;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.65	D
MetaRNN	Benign	0.0014	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.60	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.20	N;N
REVEL	Benign	0.058
Sift	Benign	0.46	T;T
Sift4G	Benign	0.88	T;T
Polyphen		0.0030	B;B
Vest4		0.038
MPC		0.049
ClinPred		0.0096	T
GERP RS		5.8
Varity_R		0.11
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

LitVar

Other links and lift over

dbSNP: rs3748140; hg19: chr8-8999019; COSMIC: COSV60099592; COSMIC: COSV60099592;