Variant chr19-55230847-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_014931.4(PPP6R1):c.2497G>A(p.Gly833Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,607,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

PPP6R1
NM_014931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.273

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:

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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
PPP6R1	NM_014931.4 linkuse as main transcript	c.2497G>A	p.Gly833Arg	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.2497G>A	p.Gly833Arg	missense_variant	22/24	1	NM_014931.4	ENSP00000414202.1	Q9UPN7
PPP6R1	ENST00000587283.5 linkuse as main transcript	c.2497G>A	p.Gly833Arg	missense_variant	21/23	1		ENSP00000467521.1	Q9UPN7
PPP6R1	ENST00000587457.1 linkuse as main transcript	n.1492G>A		non_coding_transcript_exon_variant	5/7	2
MIR6804	ENST00000614724.1 linkuse as main transcript	n.*38G>A		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152030

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000121

AC:

AN:

239042

Hom.:

AF XY:

0.000130

AC XY:

AN XY:

130966

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000560

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000249

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

148

AN:

1455128

Hom.:

Cov.:

AF XY:

0.0000912

AC XY:

AN XY:

724002

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.0000672

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000580

Gnomad4 FIN exome

AF:

0.0000206

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.000216

GnomAD4 genome

AF:

0.000131

AC:

AN:

152148

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.0000963

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000241

AC:

ExAC

AF:

0.000116

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

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

Jul 09, 2021

The c.2497G>A (p.G833R) 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 2497, causing the glycine (G) at amino acid position 833 to be replaced by an arginine (R). 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

0.073

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.031

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

L;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.49

N;.

REVEL

Benign

0.021

Sift

Uncertain

0.0070

D;.

Sift4G

Benign

0.44

T;T

Polyphen

0.0090

B;B

Vest4

0.13

MutPred

0.38

Gain of solvent accessibility (P = 0.0097);Gain of solvent accessibility (P = 0.0097);

MVP

0.043

MPC

0.063

ClinPred

0.036

GERP RS

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.39

Position offset: 5

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