Variant 9-125189579-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002721.5(PPP6C):c.75+65C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000292 in 1,607,084 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

PPP6C
NM_002721.5 intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.241

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.059919477).

BS2

High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PPP6C	NM_002721.5 linkuse as main transcript	c.75+65C>T		intron_variant		ENST00000373547.9
PPP6C	NM_001123355.2 linkuse as main transcript	c.140C>T	p.Ser47Phe	missense_variant	1/8
PPP6C	XM_047423566.1 linkuse as main transcript	c.140C>T	p.Ser47Phe	missense_variant	1/7
PPP6C	NM_001123369.2 linkuse as main transcript	c.75+65C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP6C	ENST00000373547.9 linkuse as main transcript	c.75+65C>T		intron_variant		1	NM_002721.5	P1	O00743-1
PPP6C	ENST00000451402.5 linkuse as main transcript	c.140C>T	p.Ser47Phe	missense_variant	1/8	2			O00743-3
PPP6C	ENST00000415905.5 linkuse as main transcript	c.75+65C>T		intron_variant		2			O00743-2
PPP6C	ENST00000456642.1 linkuse as main transcript	c.-55+65C>T		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000433

AC:

AN:

230854

Hom.:

AF XY:

0.0000314

AC XY:

AN XY:

127392

show subpopulations

Gnomad AFR exome

AF:

0.000296

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000173

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000197

Gnomad OTH exome

AF:

0.000178

GnomAD4 exome

AF:

0.0000268

AC:

AN:

1454882

Hom.:

Cov.:

AF XY:

0.0000235

AC XY:

AN XY:

723730

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000228

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000991

Gnomad4 OTH exome

AF:

0.000250

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000579

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 02, 2023

The c.140C>T (p.S47F) alteration is located in exon 1 (coding exon 1) of the PPP6C gene. This alteration results from a C to T substitution at nucleotide position 140, causing the serine (S) at amino acid position 47 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.47

Cadd

Benign

8.6

Dann

Uncertain

0.98

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.38

M_CAP

Benign

0.047

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-0.16

REVEL

Benign

0.049

Sift

Benign

0.036

Sift4G

Uncertain

0.030

Polyphen

0.52

Vest4

0.27

MutPred

0.31

Loss of disorder (P = 0.011);

MVP

0.17

MPC

0.96

ClinPred

0.072

GERP RS

3.8

gMVP

0.32

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over