Variant 11-68567047-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000393800.7(PPP6R3):c.1009G>C(p.Asp337His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000429 in 1,399,140 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000043 ( 0 hom. )

Consequence

PPP6R3
ENST00000393800.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.52

Variant links:

Genes affected

PPP6R3 (HGNC:1173): (protein phosphatase 6 regulatory subunit 3) Protein phosphatase regulatory subunits, such as SAPS3, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS3 is a regulatory subunit for the protein phosphatase-6 catalytic subunit (PPP6C; MIM 612725) (Stefansson and Brautigan, 2006 [PubMed 16769727]).[supplied by OMIM, Nov 2010]

PPP6R3 links:

PPP6R3 (HGNC:):

PPP6R3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6R3	NM_001164161.2 linkuse as main transcript	c.1009G>C	p.Asp337His	missense_variant	10/24	ENST00000393800.7	NP_001157633.1	Q5H9R7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP6R3	ENST00000393800.7 linkuse as main transcript	c.1009G>C	p.Asp337His	missense_variant	10/24	1	NM_001164161.2	ENSP00000377389.2		Q5H9R7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000191

AC:

AN:

157042

Hom.:

AF XY:

0.0000241

AC XY:

AN XY:

83048

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000122

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000429

AC:

AN:

1399140

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

690044

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000227

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

Sep 29, 2023

The c.1009G>C (p.D337H) alteration is located in exon 10 (coding exon 8) of the PPP6R3 gene. This alteration results from a G to C substitution at nucleotide position 1009, causing the aspartic acid (D) at amino acid position 337 to be replaced by a histidine (H). 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

Pathogenic

0.60

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Pathogenic

0.22

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.074

T;T;.;T;.;.;T;T

Eigen

Uncertain

0.68

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

D;D;D;D;D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Uncertain

0.71

D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.54

MutationAssessor

Uncertain

2.1

M;.;M;.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-3.4

D;N;D;D;D;D;D;D

REVEL

Uncertain

0.43

Sift

Uncertain

0.0050

D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.037

D;T;D;D;D;D;D;D

Polyphen

0.49

P;D;P;.;D;D;.;.

Vest4

0.68

MutPred

0.60

Gain of MoRF binding (P = 0.1497);.;Gain of MoRF binding (P = 0.1497);Gain of MoRF binding (P = 0.1497);Gain of MoRF binding (P = 0.1497);Gain of MoRF binding (P = 0.1497);Gain of MoRF binding (P = 0.1497);.;

MVP

0.55

MPC

0.48

ClinPred

0.70

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.30

gMVP

0.62

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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