Variant 7-113878102-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002711.4(PPP1R3A):c.2990T>G(p.Phe997Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00189 in 1,613,378 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 2 hom. )

Consequence

PPP1R3A
NM_002711.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.244

Variant links:

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]

PPP1R3A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011568487).

BP6

Variant 7-113878102-A-C is Benign according to our data. Variant chr7-113878102-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 549557.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-113878102-A-C is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 2 Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3A	NM_002711.4 link	c.2990T>G	p.Phe997Cys	missense_variant	Exon 4 of 4	ENST00000284601.4	NP_002702.2	Q16821-1
PPP1R3A	XM_005250473.4 link	c.2387T>G	p.Phe796Cys	missense_variant	Exon 5 of 5		XP_005250530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R3A	ENST00000284601.4 link	c.2990T>G	p.Phe997Cys	missense_variant	Exon 4 of 4	1	NM_002711.4	ENSP00000284601.3		Q16821-1

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

237

AN:

151956

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00256

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00136

AC:

339

AN:

250096

Hom.:

AF XY:

0.00141

AC XY:

191

AN XY:

135304

show subpopulations

Gnomad AFR exome

AF:

0.000312

Gnomad AMR exome

AF:

0.00133

Gnomad ASJ exome

AF:

0.00189

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.00224

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.00192

AC:

2811

AN:

1461304

Hom.:

Cov.:

AF XY:

0.00188

AC XY:

1366

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.000688

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000928

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.00229

Gnomad4 OTH exome

AF:

0.00176

GnomAD4 genome

AF:

0.00155

AC:

235

AN:

152074

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

106

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00256

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00227

Hom.:

Bravo

AF:

0.00155

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00198

AC:

ExAC

AF:

0.00119

AC:

145

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00278

EpiControl

AF:

0.00296

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Monogenic diabetes

Benign:1

Mar 10, 2017

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG Criteria:BP4 (7 predictors), BS2 (10 cases and 9 controls in T2DM) -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.29

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.47

M_CAP

Benign

0.011

MetaRNN

Benign

0.012

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.7

REVEL

Benign

0.064

Sift

Uncertain

0.0010

Sift4G

Benign

0.29

Polyphen

0.99

Vest4

0.32

MVP

0.56

MPC

0.29

ClinPred

0.025

GERP RS

1.4

Varity_R

0.16

gMVP

0.36

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over