rs854524

chr7-95269499-G-Achr7-95269499-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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 (★).

• Frequency:
  • Genomes: 𝑓 0.59 (26943 hom., cov: 32)
  • Exomes 𝑓: 0.55 (212716 hom.)
• Consequence: PPP1R9A NM_001166160.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72

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]

ACMG classification

Verdict is Benign. Variant got -14 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 criteria_provided_single_submitter, 1 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	UniProt
PPP1R9A	NM_001166160.2	c.3116G>A	p.Arg1039Gln	missense_variant	14/20	ENST00000433360.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R9A	ENST00000433360.6	c.3116G>A	p.Arg1039Gln	missense_variant	14/20	1	NM_001166160.2

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89842 AN: 151830 Hom.: 26919 Cov.: 32

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

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.: 42 AF XY: 0.545 AC XY: 383289 AN XY: 702748

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.: 32 AF XY: 0.590 AC XY: 43800 AN XY: 74250

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: criteria provided, single submitter

Submissions by phenotype

PPP1R9A-related disorder Benign:1

Benign, criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	16
Dann	Benign	0.41
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.0092	N
LIST_S2	Benign	0.48	T;.;T;T
MetaRNN	Benign	0.0000073	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.28	T
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	T
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

Other links and lift over

dbSNP: rs854524; hg19: chr7-94898811; COSMIC: COSV56912578;