dbSNP rs854522: PPP1R9A:c.2666-61T>C (chr7-95268489-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001166160.2(PPP1R9A):c.2666-61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,573,008 control chromosomes in the GnomAD database, including 138,331 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10979 hom., cov: 31)

Exomes 𝑓: 0.42 ( 127352 hom. )

Consequence

PPP1R9A
NM_001166160.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.191

Publications

9 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.431 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2 link	c.2666-61T>C		intron_variant	Intron 12 of 19	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.2666-61T>C		intron_variant	Intron 12 of 19	1	NM_001166160.2	ENSP00000405514.1		Q9ULJ8-3

Frequencies

GnomAD3 genomes

AF:

0.368

AC:

55897

AN:

151846

Hom.:

10980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.231

Gnomad AMI

AF:

0.564

Gnomad AMR

AF:

0.379

Gnomad ASJ

AF:

0.560

Gnomad EAS

AF:

0.400

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.435

Gnomad OTH

AF:

0.423

GnomAD4 exome

AF:

0.420

AC:

597103

AN:

1421046

Hom.:

127352

AF XY:

0.419

AC XY:

295567

AN XY:

706250

show subpopulations

African (AFR)

AF:

0.223

AC:

7253

AN:

32552

American (AMR)

AF:

0.336

AC:

14513

AN:

43156

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

13488

AN:

24666

East Asian (EAS)

AF:

0.447

AC:

17525

AN:

39236

South Asian (SAS)

AF:

0.326

AC:

26950

AN:

82586

European-Finnish (FIN)

AF:

0.382

AC:

18959

AN:

49600

Middle Eastern (MID)

AF:

0.445

AC:

2231

AN:

5010

European-Non Finnish (NFE)

AF:

0.435

AC:

471753

AN:

1085542

Other (OTH)

AF:

0.416

AC:

24431

AN:

58698

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

16264

32528

48792

65056

81320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14280

28560

42840

57120

71400

<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:

0.368

AC:

55906

AN:

151962

Hom.:

10979

Cov.:

AF XY:

0.365

AC XY:

27133

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.231

AC:

9563

AN:

41472

American (AMR)

AF:

0.378

AC:

5771

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.560

AC:

1942

AN:

3470

East Asian (EAS)

AF:

0.401

AC:

2059

AN:

5136

South Asian (SAS)

AF:

0.321

AC:

1546

AN:

4810

European-Finnish (FIN)

AF:

0.371

AC:

3922

AN:

10558

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.435

AC:

29553

AN:

67940

Other (OTH)

AF:

0.422

AC:

890

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1736

3473

5209

6946

8682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<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:

0.416

Hom.:

17904

Bravo

AF:

0.366

Asia WGS

AF:

0.340

AC:

1186

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.7

(source)

DANN

Benign

0.64

PhyloP100

0.19

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Computational scores

Splicing

Publications

Other links and lift over