Variant 19-55230816-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014931.4(PPP6R1):c.2528G>A(p.Gly843Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPP6R1
NM_014931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.815

Variant links:

Genes affected

PPP6R1 (HGNC:29195): (protein phosphatase 6 regulatory subunit 1) Protein phosphatase regulatory subunits, such as SAPS1, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS1 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]

PPP6R1 links:

PPP6R1 (HGNC:):

PPP6R1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05401209).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6R1	NM_014931.4 linkuse as main transcript	c.2528G>A	p.Gly843Glu	missense_variant	22/24	ENST00000412770.7	NP_055746.3	Q9UPN7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPP6R1	ENST00000412770.7 linkuse as main transcript	c.2528G>A	p.Gly843Glu	missense_variant	22/24	1	NM_014931.4	ENSP00000414202.1	Q9UPN7
PPP6R1	ENST00000587283.5 linkuse as main transcript	c.2528G>A	p.Gly843Glu	missense_variant	21/23	1		ENSP00000467521.1	Q9UPN7
PPP6R1	ENST00000587457.1 linkuse as main transcript	n.1523G>A		non_coding_transcript_exon_variant	5/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

722430

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

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

Mar 31, 2023

The c.2528G>A (p.G843E) alteration is located in exon 22 (coding exon 21) of the PPP6R1 gene. This alteration results from a G to A substitution at nucleotide position 2528, causing the glycine (G) at amino acid position 843 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

0.069

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.74

.;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.25

N;.

REVEL

Benign

0.060

Sift

Uncertain

0.015

D;.

Sift4G

Benign

0.49

T;T

Polyphen

0.0060

B;B

Vest4

0.24

MutPred

0.29

Gain of solvent accessibility (P = 0.0074);Gain of solvent accessibility (P = 0.0074);

MVP

0.068

MPC

0.068

ClinPred

0.23

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.067

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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