rs149701175

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002711.4(PPP1R3A):c.3044A>G(p.Asn1015Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,613,348 control chromosomes in the GnomAD database, including 27 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 Benign (★★).

Frequency

Genomes: 𝑓 0.0074 ( 13 hom., cov: 32)

Exomes 𝑓: 0.00073 ( 14 hom. )

Consequence

PPP1R3A
NM_002711.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.214

Publications

2 publications found

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 Gene-Disease associations (from GenCC):

diabetes mellitus, noninsulin-dependent
Inheritance: Unknown Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

PPP1R3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026070774).

BP6

Variant 7-113878048-T-C is Benign according to our data. Variant chr7-113878048-T-C is described in ClinVar as Benign. ClinVar VariationId is 393400.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00735 (1118/152046) while in subpopulation AFR AF = 0.0249 (1032/41504). AF 95% confidence interval is 0.0236. There are 13 homozygotes in GnomAd4. There are 515 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 13 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3A	NM_002711.4 link	c.3044A>G	p.Asn1015Ser	missense_variant	Exon 4 of 4	ENST00000284601.4	NP_002702.2	Q16821-1
PPP1R3A	XM_005250473.4 link	c.2441A>G	p.Asn814Ser	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.3044A>G	p.Asn1015Ser	missense_variant	Exon 4 of 4	1	NM_002711.4	ENSP00000284601.3		Q16821-1

Frequencies

GnomAD3 genomes

AF:

0.00730

AC:

1109

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0247

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00467

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00194

AC:

486

AN:

250532

AF XY:

0.00141

show subpopulations

Gnomad AFR exome

AF:

0.0259

Gnomad AMR exome

AF:

0.00168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000983

GnomAD4 exome

AF:

0.000728

AC:

1064

AN:

1461302

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

447

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.0258

AC:

862

AN:

33450

American (AMR)

AF:

0.00163

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26110

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53346

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000117

AC:

AN:

1111680

Other (OTH)

AF:

0.00169

AC:

102

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

146

218

291

364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00735

AC:

1118

AN:

152046

Hom.:

Cov.:

AF XY:

0.00693

AC XY:

515

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0249

AC:

1032

AN:

41504

American (AMR)

AF:

0.00467

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.000414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

67946

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

108

162

216

270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00246

Hom.:

Bravo

AF:

0.00801

ESP6500AA

AF:

0.0229

AC:

101

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00242

AC:

294

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Monogenic diabetes

Benign:1

Dec 21, 2018

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

ACMG criteria: BS2 (74 cases and 66 controls in T2DM), BA1 (2.6% MAF in gnomAD African)= benign; 4 homozygous in ExAC (REVEL 0.204 + 9 BP4 predictors: conflicting evidence, not using) -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.048

BayesDel_addAF

Benign

-0.78

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.87

(source)

DANN

Benign

0.099

DEOGEN2

Benign

0.092

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.24

MetaRNN

Benign

0.0026

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.1

PhyloP100

0.21

PrimateAI

Benign

0.25

PROVEAN

Benign

1.0

REVEL

Benign

0.21

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.053

MVP

0.17

MPC

0.038

ClinPred

0.0038

GERP RS

3.5

Varity_R

0.030

gMVP

0.060

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over