Genetic Variant PPP1R9A:p.Arg1039Pro (chr7-95269499-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001166160.2(PPP1R9A):c.3116G>C(p.Arg1039Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000163 in 1,408,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1039Q) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

PPP1R9A
NM_001166160.2 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0716002).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001166160.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PPP1R9A	NM_001166160.2	MANE Select	c.3116G>C	p.Arg1039Pro	missense	Exon 14 of 20	NP_001159632.1
PPP1R9A	NM_001166161.1		c.2996G>C	p.Arg999Pro	missense	Exon 12 of 18	NP_001159633.1
PPP1R9A	NM_001166162.1		c.3050G>C	p.Arg1017Pro	missense	Exon 12 of 17	NP_001159634.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PPP1R9A	ENST00000433360.6	TSL:1 MANE Select	c.3116G>C	p.Arg1039Pro	missense	Exon 14 of 20	ENSP00000405514.1
PPP1R9A	ENST00000289495.7	TSL:1	c.2996G>C	p.Arg999Pro	missense	Exon 12 of 18	ENSP00000289495.7
PPP1R9A	ENST00000456331.6	TSL:1	c.3050G>C	p.Arg1017Pro	missense	Exon 12 of 17	ENSP00000402893.2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000163

AC:

AN:

1408888

Hom.:

Cov.:

AF XY:

0.0000171

AC XY:

AN XY:

703218

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32204

American (AMR)

AF:

0.00

AC:

AN:

43634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25870

East Asian (EAS)

AF:

0.00

AC:

AN:

39428

South Asian (SAS)

AF:

0.00

AC:

AN:

84464

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.0000204

AC:

AN:

1079550

Other (OTH)

AF:

0.0000170

AC:

AN:

58990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.96

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.65

M_CAP

Benign

0.015

MetaRNN

Benign

0.072

MetaSVM

Benign

-1.0

PhyloP100

1.7

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.65

REVEL

Benign

0.030

Sift

Uncertain

0.0070

Sift4G

Benign

0.23

Vest4

0.13

MVP

0.15

MPC

0.24

ClinPred

0.17

GERP RS

2.5

gMVP

0.21

Mutation Taster

=80/20

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over