dbSNP rs7019234: PPP6C:c.670-1564T>C (chr9-125151485-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002721.5(PPP6C):c.670-1564T>C variant causes a intron change. The variant allele was found at a frequency of 0.423 in 790,136 control chromosomes in the GnomAD database, including 73,586 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 0.44 ( 15267 hom., cov: 33)

Exomes 𝑓: 0.42 ( 58319 hom. )

Consequence

PPP6C
NM_002721.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.99

Publications

6 publications found

Variant links:

Genes affected

PPP6C (HGNC:9323): (protein phosphatase 6 catalytic subunit) This gene encodes the catalytic subunit of protein phosphatase, a component of a signaling pathway regulating cell cycle progression. Splice variants encoding different protein isoforms exist. The pseudogene of this gene is located on chromosome X. [provided by RefSeq, Jul 2008]

PPP6C links:

PRPS1P2 (HGNC:9464): (phosphoribosyl pyrophosphate synthetase 1 pseudogene 2)

PRPS1P2 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=-0.51).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002721.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP6C	NM_002721.5	MANE Select	c.670-1564T>C	intron	N/A	NP_002712.1	A0A024R861
PPP6C	NM_001123355.2		c.781-1564T>C	intron	N/A	NP_001116827.1	O00743-3
PPP6C	NM_001123369.2		c.604-1564T>C	intron	N/A	NP_001116841.1	O00743-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PPP6C	ENST00000373547.9	TSL:1 MANE Select	c.670-1564T>C	intron	N/A	ENSP00000362648.4	O00743-1
PPP6C	ENST00000451402.5	TSL:2	c.781-1564T>C	intron	N/A	ENSP00000392147.1	O00743-3
PPP6C	ENST00000889868.1		c.715-1564T>C	intron	N/A	ENSP00000559927.1

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67225

AN:

151950

Hom.:

15246

Cov.:

show subpopulations

Gnomad AFR

AF:

0.476

Gnomad AMI

AF:

0.472

Gnomad AMR

AF:

0.370

Gnomad ASJ

AF:

0.508

Gnomad EAS

AF:

0.528

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.293

Gnomad MID

AF:

0.414

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.441

GnomAD4 exome

AF:

0.418

AC:

266910

AN:

638068

Hom.:

58319

Cov.:

AF XY:

0.420

AC XY:

145406

AN XY:

345794

show subpopulations

African (AFR)

AF:

0.473

AC:

8377

AN:

17692

American (AMR)

AF:

0.255

AC:

10729

AN:

42082

Ashkenazi Jewish (ASJ)

AF:

0.502

AC:

9975

AN:

19858

East Asian (EAS)

AF:

0.534

AC:

19214

AN:

35956

South Asian (SAS)

AF:

0.391

AC:

26456

AN:

67728

European-Finnish (FIN)

AF:

0.297

AC:

15357

AN:

51756

Middle Eastern (MID)

AF:

0.459

AC:

1869

AN:

4068

European-Non Finnish (NFE)

AF:

0.439

AC:

160508

AN:

365922

Other (OTH)

AF:

0.437

AC:

14425

AN:

33006

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

7401

14802

22202

29603

37004

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1188

2376

3564

4752

5940

<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:

0.442

AC:

67286

AN:

152068

Hom.:

15267

Cov.:

AF XY:

0.433

AC XY:

32212

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.476

AC:

19726

AN:

41466

American (AMR)

AF:

0.370

AC:

5647

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.508

AC:

1762

AN:

3468

East Asian (EAS)

AF:

0.528

AC:

2726

AN:

5160

South Asian (SAS)

AF:

0.411

AC:

1977

AN:

4814

European-Finnish (FIN)

AF:

0.293

AC:

3102

AN:

10600

Middle Eastern (MID)

AF:

0.414

AC:

121

AN:

292

European-Non Finnish (NFE)

AF:

0.454

AC:

30849

AN:

67966

Other (OTH)

AF:

0.448

AC:

947

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1925

3850

5775

7700

9625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.432

Hom.:

3079

Bravo

AF:

0.451

Asia WGS

AF:

0.495

AC:

1721

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.4

(source)

DANN

Benign

0.78

PhyloP100

5.0

Mutation Taster

=95/5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over