dbSNP rs854524: PPP1R9A:p.Arg1039Gln (chr7-95269499-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001166160.2(PPP1R9A):c.3116G>A(p.Arg1039Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 1,559,756 control chromosomes in the GnomAD database, including 239,659 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.59 ( 26943 hom., cov: 32)

Exomes 𝑓: 0.55 ( 212716 hom. )

Consequence

PPP1R9A
NM_001166160.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.72

Publications

33 publications found

Variant links:

Genes affected

PPP1R9A (HGNC:14946): (protein phosphatase 1 regulatory subunit 9A) This gene is imprinted, and located in a cluster of imprinted genes on chromosome 7q12. This gene is transcribed in both neuronal and multiple embryonic tissues, and it is maternally expressed mainly in embryonic skeletal muscle tissues and biallelically expressed in other embryonic tissues. The protein encoded by this gene includes a PDZ domain and a sterile alpha motif (SAM). It is a regulatory subunit of protein phosphatase I, and controls actin cytoskeleton reorganization. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

PPP1R9A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.3233136E-6).

BP6

Variant 7-95269499-G-A is Benign according to our data. Variant chr7-95269499-G-A is described in ClinVar as Benign. ClinVar VariationId is 3058883.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2 link	c.3116G>A	p.Arg1039Gln	missense_variant	Exon 14 of 20	ENST00000433360.6	NP_001159632.1	Q9ULJ8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R9A	ENST00000433360.6 link	c.3116G>A	p.Arg1039Gln	missense_variant	Exon 14 of 20	1	NM_001166160.2	ENSP00000405514.1		Q9ULJ8-3

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89842

AN:

151830

Hom.:

26919

Cov.:

show subpopulations

Gnomad AFR

AF:

0.681

Gnomad AMI

AF:

0.704

Gnomad AMR

AF:

0.615

Gnomad ASJ

AF:

0.657

Gnomad EAS

AF:

0.642

Gnomad SAS

AF:

0.503

Gnomad FIN

AF:

0.525

Gnomad MID

AF:

0.623

Gnomad NFE

AF:

0.539

Gnomad OTH

AF:

0.625

GnomAD2 exomes

AF:

0.574

AC:

133240

AN:

232092

AF XY:

0.566

show subpopulations

Gnomad AFR exome

AF:

0.679

Gnomad AMR exome

AF:

0.635

Gnomad ASJ exome

AF:

0.651

Gnomad EAS exome

AF:

0.655

Gnomad FIN exome

AF:

0.529

Gnomad NFE exome

AF:

0.544

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.547

AC:

770745

AN:

1407808

Hom.:

212716

Cov.:

AF XY:

0.545

AC XY:

383289

AN XY:

702748

show subpopulations

African (AFR)

AF:

0.675

AC:

21704

AN:

32172

American (AMR)

AF:

0.632

AC:

27535

AN:

43574

Ashkenazi Jewish (ASJ)

AF:

0.646

AC:

16708

AN:

25864

East Asian (EAS)

AF:

0.688

AC:

27119

AN:

39398

South Asian (SAS)

AF:

0.503

AC:

42414

AN:

84384

European-Finnish (FIN)

AF:

0.538

AC:

21038

AN:

39086

Middle Eastern (MID)

AF:

0.602

AC:

3410

AN:

5662

European-Non Finnish (NFE)

AF:

0.536

AC:

577691

AN:

1078714

Other (OTH)

AF:

0.562

AC:

33126

AN:

58954

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

17454

34908

52363

69817

87271

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16380

32760

49140

65520

81900

<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:

0.592

AC:

89914

AN:

151948

Hom.:

26943

Cov.:

AF XY:

0.590

AC XY:

43800

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.680

AC:

28209

AN:

41454

American (AMR)

AF:

0.615

AC:

9377

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.657

AC:

2278

AN:

3468

East Asian (EAS)

AF:

0.641

AC:

3315

AN:

5168

South Asian (SAS)

AF:

0.502

AC:

2423

AN:

4822

European-Finnish (FIN)

AF:

0.525

AC:

5532

AN:

10540

Middle Eastern (MID)

AF:

0.633

AC:

186

AN:

294

European-Non Finnish (NFE)

AF:

0.539

AC:

36632

AN:

67948

Other (OTH)

AF:

0.627

AC:

1320

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1869

3739

5608

7478

9347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.566

Hom.:

72529

Bravo

AF:

0.607

TwinsUK

AF:

0.536

AC:

1986

ALSPAC

AF:

0.547

AC:

2107

ESP6500AA

AF:

0.679

AC:

2128

ESP6500EA

AF:

0.557

AC:

3991

ExAC

AF:

0.572

AC:

67625

Asia WGS

AF:

0.595

AC:

2074

AN:

3478

EpiCase

AF:

0.552

EpiControl

AF:

0.555

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPP1R9A-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.41

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.48

T;.;T;T

MetaRNN

Benign

0.0000073

T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

1.7

PrimateAI

Benign

0.28

PROVEAN

Benign

0.81

N;N;N;N

REVEL

Benign

0.026

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.59

T;T;T;T

Vest4

0.045

MPC

0.19

ClinPred

0.0049

GERP RS

2.5

gMVP

0.12

Mutation Taster

=98/2

polymorphism (auto)

(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