Variant 11-68569751-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001164161.2(PPP6R3):c.1132A>G(p.Met378Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000211 in 1,420,610 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: 0.0000021 ( 0 hom. )

Consequence

PPP6R3
NM_001164161.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.63

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:

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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.1132A>G	p.Met378Val	missense_variant	11/24	ENST00000393800.7	NP_001157633.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP6R3	ENST00000393800.7 linkuse as main transcript	c.1132A>G	p.Met378Val	missense_variant	11/24	1	NM_001164161.2	ENSP00000377389	P4	Q5H9R7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1420610

Hom.:

Cov.:

AF XY:

0.00000285

AC XY:

AN XY:

702500

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000184

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 19, 2022

The c.1132A>G (p.M378V) alteration is located in exon 11 (coding exon 9) of the PPP6R3 gene. This alteration results from a A to G substitution at nucleotide position 1132, causing the methionine (M) at amino acid position 378 to be replaced by a valine (V). 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

0.66

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.073

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

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.34

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

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

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.70

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

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.3

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

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.5

N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.27

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.0060

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

Polyphen

0.036

B;P;B;.;B;B;B;B;.;.

Vest4

0.91

MutPred

0.77

Gain of ubiquitination at K381 (P = 0.1103);.;Gain of ubiquitination at K381 (P = 0.1103);Gain of ubiquitination at K381 (P = 0.1103);Gain of ubiquitination at K381 (P = 0.1103);Gain of ubiquitination at K381 (P = 0.1103);.;.;Gain of ubiquitination at K381 (P = 0.1103);.;

MVP

0.52

MPC

0.39

ClinPred

0.86

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.43

gMVP

0.78

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over