Variant 19-55231479-G-A 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.2390C>T(p.Ala797Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000622 in 1,608,004 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

PPP6R1
NM_014931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.241

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=0.061199695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6R1	NM_014931.4 linkuse as main transcript	c.2390C>T	p.Ala797Val	missense_variant	21/24	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.2390C>T	p.Ala797Val	missense_variant	21/24	1	NM_014931.4	ENSP00000414202.1	Q9UPN7
PPP6R1	ENST00000587283.5 linkuse as main transcript	c.2390C>T	p.Ala797Val	missense_variant	20/23	1		ENSP00000467521.1	Q9UPN7
PPP6R1	ENST00000587457.1 linkuse as main transcript	n.1385C>T		non_coding_transcript_exon_variant	4/7	2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152114

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000169

AC:

AN:

237026

Hom.:

AF XY:

0.0000233

AC XY:

AN XY:

128966

show subpopulations

Gnomad AFR exome

AF:

0.0000723

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000171

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:

0.00000618

AC:

AN:

1455890

Hom.:

Cov.:

AF XY:

0.00000829

AC XY:

AN XY:

723560

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000828

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

Jul 11, 2023

The c.2390C>T (p.A797V) alteration is located in exon 21 (coding exon 20) of the PPP6R1 gene. This alteration results from a C to T substitution at nucleotide position 2390, causing the alanine (A) at amino acid position 797 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

Benign

0.087

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

T;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.79

.;T

M_CAP

Benign

0.034

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.38

N;.

REVEL

Benign

0.042

Sift

Uncertain

0.014

D;.

Sift4G

Benign

0.34

T;T

Polyphen

0.0010

B;B

Vest4

0.26

MutPred

0.31

Gain of catalytic residue at A797 (P = 0.0833);Gain of catalytic residue at A797 (P = 0.0833);

MVP

0.13

MPC

0.11

ClinPred

0.13

GERP RS

2.7

Varity_R

0.038

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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