Variant 6-30602227-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000376511.7(PPP1R10):c.2422A>C(p.Ser808Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000075 in 1,600,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PPP1R10
ENST00000376511.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.281

Variant links:

Genes affected

PPP1R10 (HGNC:9284): (protein phosphatase 1 regulatory subunit 10) This gene encodes a protein phosphatase 1 binding protein. The encoded protein plays a role in many cellular processes including cell cycle progression, DNA repair and apoptosis by regulating the activity of protein phosphatase 1. This gene lies within the major histocompatibility complex class I region on chromosome 6, and alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jul 2012]

PPP1R10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07514748).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PPP1R10	NM_002714.4 linkuse as main transcript	c.2422A>C	p.Ser808Arg	missense_variant	19/20	ENST00000376511.7	NP_002705.2
PPP1R10	NM_001376195.1 linkuse as main transcript	c.2422A>C	p.Ser808Arg	missense_variant	19/20		NP_001363124.1
PPP1R10	XM_011514722.2 linkuse as main transcript	c.2422A>C	p.Ser808Arg	missense_variant	20/21		XP_011513024.1
PPP1R10	NR_072994.2 linkuse as main transcript	n.2913A>C		non_coding_transcript_exon_variant	19/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R10	ENST00000376511.7 linkuse as main transcript	c.2422A>C	p.Ser808Arg	missense_variant	19/20	1	NM_002714.4	ENSP00000365694	P1

Frequencies

GnomAD3 genomes

AF:

0.00000697

AC:

AN:

143416

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000152

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000755

AC:

AN:

1457566

Hom.:

Cov.:

AF XY:

0.00000690

AC XY:

AN XY:

724910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000991

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000697

AC:

AN:

143416

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

69944

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000152

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

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 14, 2023

The c.2422A>C (p.S808R) alteration is located in exon 19 (coding exon 17) of the PPP1R10 gene. This alteration results from a A to C substitution at nucleotide position 2422, causing the serine (S) at amino acid position 808 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.063

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.62

M_CAP

Benign

0.0054

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.77

PROVEAN

Benign

0.35

REVEL

Benign

0.022

Sift

Benign

0.045

Sift4G

Benign

0.29

Polyphen

0.056

Vest4

0.14

MutPred

0.39

Loss of glycosylation at S808 (P = 9e-04);

MVP

0.37

MPC

0.42

ClinPred

0.063

GERP RS

1.5

Varity_R

0.049

gMVP

0.66

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

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