Variant chr6-30602065-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 ENST00000376511.7(PPP1R10):c.2584C>T(p.His862Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000212 in 1,414,382 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: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PPP1R10
ENST00000376511.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.543

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:

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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=0.131924).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
PPP1R10	NM_002714.4 linkuse as main transcript	c.2584C>T	p.His862Tyr	missense_variant	19/20	ENST00000376511.7	NP_002705.2
PPP1R10	NM_001376195.1 linkuse as main transcript	c.2584C>T	p.His862Tyr	missense_variant	19/20		NP_001363124.1
PPP1R10	XM_011514722.2 linkuse as main transcript	c.2584C>T	p.His862Tyr	missense_variant	20/21		XP_011513024.1
PPP1R10	NR_072994.2 linkuse as main transcript	n.3075C>T		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.2584C>T	p.His862Tyr	missense_variant	19/20	1	NM_002714.4	ENSP00000365694	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000212

AC:

AN:

1414382

Hom.:

Cov.:

AF XY:

0.00000430

AC XY:

AN XY:

696954

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

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 28, 2022

The c.2584C>T (p.H862Y) 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 2584, causing the histidine (H) at amino acid position 862 to be replaced by a tyrosine (Y). 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

0.14

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Benign

0.89

DEOGEN2

Benign

0.070

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.63

M_CAP

Benign

0.020

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.25

REVEL

Benign

0.035

Sift

Pathogenic

0.0

Sift4G

Benign

0.85

Polyphen

0.26

Vest4

0.49

MutPred

0.25

Gain of phosphorylation at H862 (P = 0.0056);

MVP

0.22

MPC

0.43

ClinPred

0.37

GERP RS

3.5

Varity_R

0.11

gMVP

0.25

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over