6-30602601-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_002714.4(PPP1R10):c.2048C>T(p.Pro683Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,575,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

PPP1R10
NM_002714.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.33

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 -5 ACMG points.

PP2

Missense variant where missense usually causes diseases, PPP1R10

BP4

Computational evidence support a benign effect (MetaRNN=0.18509632).

BS2

High AC in GnomAd at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PPP1R10	NM_002714.4 linkuse as main transcript	c.2048C>T	p.Pro683Leu	missense_variant	19/20	ENST00000376511.7
PPP1R10	NM_001376195.1 linkuse as main transcript	c.2048C>T	p.Pro683Leu	missense_variant	19/20
PPP1R10	XM_011514722.2 linkuse as main transcript	c.2048C>T	p.Pro683Leu	missense_variant	20/21
PPP1R10	NR_072994.2 linkuse as main transcript	n.2539C>T		non_coding_transcript_exon_variant	19/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R10	ENST00000376511.7 linkuse as main transcript	c.2048C>T	p.Pro683Leu	missense_variant	19/20	1	NM_002714.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0000534

AC:

AN:

149908

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000984

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:

0.0000446

Gnomad OTH

AF:

0.000485

GnomAD3 exomes

AF:

0.0000399

AC:

AN:

200624

Hom.:

AF XY:

0.0000271

AC XY:

AN XY:

110606

show subpopulations

Gnomad AFR exome

AF:

0.000160

Gnomad AMR exome

AF:

0.0000369

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000406

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000439

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000126

AC:

AN:

1425338

Hom.:

Cov.:

AF XY:

0.00000566

AC XY:

AN XY:

706954

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000264

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000245

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000128

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

AF:

0.0000534

AC:

AN:

149908

Hom.:

Cov.:

AF XY:

0.0000683

AC XY:

AN XY:

73206

show subpopulations

Gnomad4 AFR

AF:

0.0000984

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:

0.0000446

Gnomad4 OTH

AF:

0.000485

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000367

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000342

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

May 05, 2023

The c.2048C>T (p.P683L) alteration is located in exon 19 (coding exon 17) of the PPP1R10 gene. This alteration results from a C to T substitution at nucleotide position 2048, causing the proline (P) at amino acid position 683 to be replaced by a leucine (L). 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

0.28

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.38

Cadd

Uncertain

Dann

Benign

0.93

DEOGEN2

Benign

0.23

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.61

M_CAP

Benign

0.018

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-2.0

REVEL

Benign

0.11

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.015

Polyphen

0.0080

Vest4

0.56

MVP

0.25

MPC

0.38

ClinPred

0.15

GERP RS

3.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.8

Varity_R

0.26

gMVP

0.36

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