Variant rs854524 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 12/17 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

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 made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2 link	c.3116G>A	p.Arg1039Gln	missense_variant	14/20	ENST00000433360.6	NP_001159632.1	Q9ULJ8-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R9A	ENST00000433360.6 link	c.3116G>A	p.Arg1039Gln	missense_variant	14/20	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

GnomAD3 exomes

AF:

0.574

AC:

133240

AN:

232092

Hom.:

38728

AF XY:

0.566

AC XY:

71813

AN XY:

126980

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 SAS exome

AF:

0.505

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

Gnomad4 AFR exome

AF:

0.675

Gnomad4 AMR exome

AF:

0.632

Gnomad4 ASJ exome

AF:

0.646

Gnomad4 EAS exome

AF:

0.688

Gnomad4 SAS exome

AF:

0.503

Gnomad4 FIN exome

AF:

0.538

Gnomad4 NFE exome

AF:

0.536

Gnomad4 OTH exome

AF:

0.562

GnomAD4 genome

AF:

0.592

AC:

89914

AN:

151948

Hom.:

26943

Cov.:

AF XY:

0.590

AC XY:

43800

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.680

Gnomad4 AMR

AF:

0.615

Gnomad4 ASJ

AF:

0.657

Gnomad4 EAS

AF:

0.641

Gnomad4 SAS

AF:

0.502

Gnomad4 FIN

AF:

0.525

Gnomad4 NFE

AF:

0.539

Gnomad4 OTH

AF:

0.627

Alfa

AF:

0.560

Hom.:

51881

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

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 17, 2019

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

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

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

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

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