Variant chr19-55230670-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014931.4(PPP6R1):c.2585C>T(p.Thr862Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,449,036 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: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

PPP6R1
NM_014931.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0440

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08946985).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP6R1	NM_014931.4 linkuse as main transcript	c.2585C>T	p.Thr862Met	missense_variant	23/24	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.2585C>T	p.Thr862Met	missense_variant	23/24	1	NM_014931.4	ENSP00000414202.1	Q9UPN7
PPP6R1	ENST00000587283.5 linkuse as main transcript	c.2585C>T	p.Thr862Met	missense_variant	22/23	1		ENSP00000467521.1	Q9UPN7
PPP6R1	ENST00000587457.1 linkuse as main transcript	n.1580C>T		non_coding_transcript_exon_variant	6/7	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1449036

Hom.:

Cov.:

AF XY:

0.0000139

AC XY:

AN XY:

719638

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000934

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000509

Gnomad4 SAS exome

AF:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000452

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000612

Hom.:

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

Dec 15, 2023

The c.2585C>T (p.T862M) alteration is located in exon 23 (coding exon 22) of the PPP6R1 gene. This alteration results from a C to T substitution at nucleotide position 2585, causing the threonine (T) at amino acid position 862 to be replaced by a methionine (M). 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

0.074

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.70

.;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.089

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.90

N;.

REVEL

Benign

0.057

Sift

Uncertain

0.0060

D;.

Sift4G

Benign

0.11

T;T

Polyphen

0.61

P;P

Vest4

0.21

MVP

0.068

MPC

0.077

ClinPred

0.094

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.036

gMVP

0.15

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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