rs151310594

Positions:

• chr7-113878825-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2 BP4_Strong BP6_Very_Strong

The ENST00000284601.4(PPP1R3A):​c.2267C>T​(p.Pro756Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000619 in 1,613,408 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00050 (1 hom.)
• Consequence: PPP1R3A ENST00000284601.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.58

Genes affected

PPP1R3A (HGNC:9291): (protein phosphatase 1 regulatory subunit 3A) The glycogen-associated form of protein phosphatase-1 (PP1) derived from skeletal muscle is a heterodimer composed of a 37-kD catalytic subunit and a 124-kD targeting and regulatory subunit. This gene encodes the regulatory subunit which binds to muscle glycogen with high affinity, thereby enhancing dephosphorylation of glycogen-bound substrates for PP1 such as glycogen synthase and glycogen phosphorylase kinase. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0126564205).
• BP6: Variant 7-113878825-G-A is Benign according to our data. Variant chr7-113878825-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 393402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3A	NM_002711.4	c.2267C>T	p.Pro756Leu	missense_variant	4/4	ENST00000284601.4	NP_002702.2
PPP1R3A	XM_005250473.4	c.1664C>T	p.Pro555Leu	missense_variant	5/5		XP_005250530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R3A	ENST00000284601.4	c.2267C>T	p.Pro756Leu	missense_variant	4/4	1	NM_002711.4	ENSP00000284601	P1

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 260 AN: 151942 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00288

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00604

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00432

GnomAD3 exomes AF: 0.000926 AC: 232 AN: 250464 Hom.: 0 AF XY: 0.000850 AC XY: 115 AN XY: 135346

Gnomad AFR exome AF: 0.00277

Gnomad AMR exome AF: 0.00258

Gnomad ASJ exome AF: 0.00259

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000495

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.000504 AC: 736 AN: 1461348 Hom.: 1 Cov.: 71 AF XY: 0.000488 AC XY: 355 AN XY: 726974

Gnomad4 AFR exome AF: 0.00254

Gnomad4 AMR exome AF: 0.00249

Gnomad4 ASJ exome AF: 0.00230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000324

Gnomad4 OTH exome AF: 0.00159

GnomAD4 genome AF: 0.00173 AC: 263 AN: 152060 Hom.: 0 Cov.: 33 AF XY: 0.00164 AC XY: 122 AN XY: 74332

Gnomad4 AFR AF: 0.00292

Gnomad4 AMR AF: 0.00610

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.000737 Hom.: 0

Bravo AF: 0.00236

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00204 AC: 9

ESP6500EA AF: 0.000582 AC: 5

ExAC AF: 0.000750 AC: 91

EpiCase AF: 0.000491

EpiControl AF: 0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Monogenic diabetes Benign:2

Likely benign, criteria provided, single submitter	research	Biomedical Genomics and Oncogenetics Laboratory, Institut Pasteur de Tunis, University Tunis El Manar	Apr 25, 2022	- -
Likely benign, criteria provided, single submitter	research	Personalized Diabetes Medicine Program, University of Maryland School of Medicine	Oct 31, 2017	ACMG criteria: PP3 (7 predictors), BP4 (3 predictors), BS2 (23 cases and 22 controls in type2diabetesgenetics.org)=likely benign -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Uncertain	-0.020
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.013	T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	1.8	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-4.2	D
REVEL	Uncertain	0.43
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.46
MVP		0.89
MPC		0.31
ClinPred		0.031	T
GERP RS		5.9
Varity_R		0.51
gMVP		0.43

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: rs151310594; hg19: chr7-113518880;