Variant chr9-125189698-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_002721.5(PPP6C):c.21C>G(p.Asp7Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,608,892 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000021 ( 1 hom. )

Consequence

PPP6C
NM_002721.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37870455).

BS2

High AC in GnomAdExome4 at 30 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6C	NM_002721.5 linkuse as main transcript	c.21C>G	p.Asp7Glu	missense_variant	1/7	ENST00000373547.9	NP_002712.1	O00743-1A0A024R861
PPP6C	NM_001123355.2 linkuse as main transcript	c.21C>G	p.Asp7Glu	missense_variant	1/8		NP_001116827.1	O00743-3
PPP6C	NM_001123369.2 linkuse as main transcript	c.21C>G	p.Asp7Glu	missense_variant	1/6		NP_001116841.1	O00743-2
PPP6C	XM_047423566.1 linkuse as main transcript	c.21C>G	p.Asp7Glu	missense_variant	1/7		XP_047279522.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPP6C	ENST00000373547.9 linkuse as main transcript	c.21C>G	p.Asp7Glu	missense_variant	1/7	1	NM_002721.5	ENSP00000362648.4	O00743-1
PPP6C	ENST00000451402.5 linkuse as main transcript	c.21C>G	p.Asp7Glu	missense_variant	1/8	2		ENSP00000392147.1	O00743-3
PPP6C	ENST00000415905.5 linkuse as main transcript	c.21C>G	p.Asp7Glu	missense_variant	1/6	2		ENSP00000411744.1	O00743-2
PPP6C	ENST00000456642.1 linkuse as main transcript	c.-109C>G		5_prime_UTR_variant	1/6	3		ENSP00000416287.1	Q5T1S7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000206

AC:

AN:

242564

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

132062

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000459

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000206

AC:

AN:

1456672

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

724738

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000243

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

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 21, 2021

The c.21C>G (p.D7E) alteration is located in exon 1 (coding exon 1) of the PPP6C gene. This alteration results from a C to G substitution at nucleotide position 21, causing the aspartic acid (D) at amino acid position 7 to be replaced by a glutamic acid (E). 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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.039

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.044

MetaRNN

Benign

0.38

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.9

M;M;M

PrimateAI

Uncertain

0.79

PROVEAN

Uncertain

-3.3

D;D;D

REVEL

Benign

0.28

Sift

Benign

0.049

D;D;D

Sift4G

Benign

0.073

T;T;T

Polyphen

0.0080

B;B;B

Vest4

0.67

MutPred

0.58

Loss of stability (P = 0.1028);Loss of stability (P = 0.1028);Loss of stability (P = 0.1028);

MVP

0.83

MPC

1.2

ClinPred

0.88

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.63

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