8-9141677-G-C

Variant names:

• chr8-9141677-G-C
• rs330924
• NM_024607.4:c.-17-9C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 1P and 8B. PP3 BA1

The NM_024607.4(PPP1R3B):​c.-17-9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 1,593,628 control chromosomes in the GnomAD database, including 116,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (11709 hom., cov: 31)
  • Exomes 𝑓: 0.36 (104318 hom.)
• Consequence: PPP1R3B NM_024607.4 intron
• Scores: Splicing: ADA: 0.9995
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.47
• Publications: 14 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: Benign. The variant received -7 ACMG points.

• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3B	NM_024607.4	MANE Select	c.-17-9C>G		intron	N/A	NP_078883.2
	PPP1R3B	NM_001201329.2		c.-17-9C>G		intron	N/A	NP_001188258.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R3B	ENST00000310455.4	TSL:1 MANE Select	c.-17-9C>G		intron	N/A	ENSP00000308318.3
	ENSG00000254340	ENST00000520017.1	TSL:3	n.254G>C		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000254340	ENST00000522057.1	TSL:2	n.156G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57124 AN: 151830 Hom.: 11697 Cov.: 31

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.811

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.385

GnomAD2 exomes AF: 0.427 AC: 101827 AN: 238640 AF XY: 0.429

Gnomad AFR exome AF: 0.374

Gnomad AMR exome AF: 0.509

Gnomad ASJ exome AF: 0.294

Gnomad EAS exome AF: 0.804

Gnomad FIN exome AF: 0.288

Gnomad NFE exome AF: 0.334

Gnomad OTH exome AF: 0.389

GnomAD4 exome AF: 0.364 AC: 524660 AN: 1441680 Hom.: 104318 Cov.: 34 AF XY: 0.370 AC XY: 264043 AN XY: 714088

African (AFR) AF: 0.365 AC: 11983 AN: 32858

American (AMR) AF: 0.500 AC: 21567 AN: 43168

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 7419 AN: 25666

East Asian (EAS) AF: 0.801 AC: 31380 AN: 39166

South Asian (SAS) AF: 0.611 AC: 52239 AN: 85526

European-Finnish (FIN) AF: 0.295 AC: 15515 AN: 52518

Middle Eastern (MID) AF: 0.440 AC: 2499 AN: 5682

European-Non Finnish (NFE) AF: 0.328 AC: 359552 AN: 1097746

Other (OTH) AF: 0.379 AC: 22506 AN: 59350

GnomAD4 genome AF: 0.376 AC: 57195 AN: 151948 Hom.: 11709 Cov.: 31 AF XY: 0.382 AC XY: 28367 AN XY: 74260

African (AFR) AF: 0.378 AC: 15667 AN: 41438

American (AMR) AF: 0.427 AC: 6523 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3466

East Asian (EAS) AF: 0.811 AC: 4170 AN: 5144

South Asian (SAS) AF: 0.633 AC: 3051 AN: 4822

European-Finnish (FIN) AF: 0.297 AC: 3133 AN: 10548

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22407 AN: 67940

Other (OTH) AF: 0.385 AC: 814 AN: 2112

Alfa AF: 0.251 Hom.: 962

Bravo AF: 0.387

Asia WGS AF: 0.627 AC: 2174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.67
PhyloP100		3.5
Mutation Taster		=96/4	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.99
SpliceAI score (max)		0.99		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.99		Position offset: -1
DS_AL_spliceai		0.95		Position offset: -9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs330924; hg19: chr8-8999187;