7-94910228-T-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001166160.2(PPP1R9A):c.115T>A(p.Ser39Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00568 in 1,613,640 control chromosomes in the GnomAD database, including 475 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 0.030 ( 248 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 227 hom. )

Consequence

PPP1R9A
NM_001166160.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.964

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014253259).

BP6

Variant 7-94910228-T-A is Benign according to our data. Variant chr7-94910228-T-A is described in ClinVar as Benign. ClinVar VariationId is 776241.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

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	UniProt
PPP1R9A	NM_001166160.2	MANE Select	c.115T>A	p.Ser39Thr	missense	Exon 2 of 20	NP_001159632.1	Q9ULJ8-3
PPP1R9A	NM_001166161.1		c.115T>A	p.Ser39Thr	missense	Exon 1 of 18	NP_001159633.1	Q9ULJ8-5
PPP1R9A	NM_001166162.1		c.115T>A	p.Ser39Thr	missense	Exon 1 of 17	NP_001159634.1	Q9ULJ8-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PPP1R9A	ENST00000433360.6	TSL:1 MANE Select	c.115T>A	p.Ser39Thr	missense	Exon 2 of 20	ENSP00000405514.1	Q9ULJ8-3
PPP1R9A	ENST00000289495.7	TSL:1	c.115T>A	p.Ser39Thr	missense	Exon 1 of 18	ENSP00000289495.7	Q9ULJ8-5
PPP1R9A	ENST00000456331.6	TSL:1	c.115T>A	p.Ser39Thr	missense	Exon 1 of 17	ENSP00000402893.2	Q9ULJ8-4

Frequencies

GnomAD3 genomes

AF:

0.0303

AC:

4594

AN:

151704

Hom.:

246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00945

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0212

GnomAD2 exomes

AF:

0.00809

AC:

2032

AN:

251294

AF XY:

0.00576

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.00535

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000334

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00312

AC:

4563

AN:

1461820

Hom.:

227

Cov.:

AF XY:

0.00265

AC XY:

1930

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.110

AC:

3668

AN:

33478

American (AMR)

AF:

0.00608

AC:

272

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000104

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.0000375

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00277

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000181

AC:

201

AN:

1111990

Other (OTH)

AF:

0.00652

AC:

394

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

244

487

731

974

1218

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

118

236

354

472

590

<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:

0.0303

AC:

4602

AN:

151820

Hom.:

248

Cov.:

AF XY:

0.0284

AC XY:

2107

AN XY:

74184

show subpopulations

African (AFR)

AF:

0.106

AC:

4388

AN:

41362

American (AMR)

AF:

0.00943

AC:

144

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5140

South Asian (SAS)

AF:

0.00

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

67934

Other (OTH)

AF:

0.0210

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

206

411

617

822

1028

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.00462

Hom.:

Bravo

AF:

0.0342

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.101

AC:

444

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.00988

AC:

1199

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000415

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.023

Eigen

Benign

0.025

Eigen_PC

Benign

0.053

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.82

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

PhyloP100

0.96

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.2

REVEL

Benign

0.033

Sift

Benign

0.28

Sift4G

Benign

0.37

Polyphen

0.36

Vest4

0.33

MVP

0.44

MPC

0.22

ClinPred

0.0099

GERP RS

1.7

PromoterAI

-0.0046

Neutral

(source)

Varity_R

0.084

gMVP

0.11

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over