Genetic Variant PPP1R9A:c.*3776T>C (chr7-95294079-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.*3776T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 151,916 control chromosomes in the GnomAD database, including 25,302 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 0.55 ( 25295 hom., cov: 30)

Exomes 𝑓: 0.75 ( 7 hom. )

Consequence

PPP1R9A
NM_001166160.2 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.143

Publications

7 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.69 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R9A	NM_001166160.2 link	c.*3776T>C		3_prime_UTR_variant	Exon 20 of 20	ENST00000433360.6	NP_001159632.1	Q9ULJ8-3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP1R9A	ENST00000433360.6 link	c.*3776T>C	3_prime_UTR_variant	Exon 20 of 20	1	NM_001166160.2	ENSP00000405514.1	Q9ULJ8-3
PPP1R9A	ENST00000456331.6 link	c.*3776T>C	3_prime_UTR_variant	Exon 17 of 17	1		ENSP00000402893.2	Q9ULJ8-4
PPP1R9A	ENST00000340694.8 link	c.*3776T>C	3_prime_UTR_variant	Exon 16 of 16	5		ENSP00000344524.4	Q9ULJ8-1
PPP1R9A	ENST00000433881.5 link	c.*3776T>C	3_prime_UTR_variant	Exon 16 of 16	5		ENSP00000398870.1	Q9ULJ8-1

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83043

AN:

151770

Hom.:

25293

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.581

Gnomad ASJ

AF:

0.627

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.631

Gnomad FIN

AF:

0.628

Gnomad MID

AF:

0.638

Gnomad NFE

AF:

0.695

Gnomad OTH

AF:

0.569

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

Cov.:

AF XY:

0.722

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.722

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Hom

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

AF:

0.547

AC:

83055

AN:

151888

Hom.:

25295

Cov.:

AF XY:

0.545

AC XY:

40470

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.273

AC:

11318

AN:

41406

American (AMR)

AF:

0.580

AC:

8851

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.627

AC:

2176

AN:

3470

East Asian (EAS)

AF:

0.353

AC:

1817

AN:

5152

South Asian (SAS)

AF:

0.631

AC:

3042

AN:

4818

European-Finnish (FIN)

AF:

0.628

AC:

6602

AN:

10520

Middle Eastern (MID)

AF:

0.652

AC:

189

AN:

290

European-Non Finnish (NFE)

AF:

0.695

AC:

47257

AN:

67954

Other (OTH)

AF:

0.563

AC:

1188

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1665

3331

4996

6662

8327

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

706

1412

2118

2824

3530

<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:

0.644

Hom.:

85500

Bravo

AF:

0.526

Asia WGS

AF:

0.454

AC:

1578

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.2

(source)

DANN

Benign

0.54

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over