6-30602025-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2 BP4_Strong BS2

The NM_002714.4(PPP1R10):c.2624C>T(p.Pro875Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,536,312 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 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (0 hom.)
• Consequence: PPP1R10 NM_002714.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP2: Missense variant where missense usually causes diseases, PPP1R10
• BP4: Computational evidence support a benign effect (MetaRNN=0.0669702).
• BS2: High AC in GnomAd at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R10	NM_002714.4	c.2624C>T	p.Pro875Leu	missense_variant	19/20	ENST00000376511.7
PPP1R10	NM_001376195.1	c.2624C>T	p.Pro875Leu	missense_variant	19/20
PPP1R10	XM_011514722.2	c.2624C>T	p.Pro875Leu	missense_variant	20/21
PPP1R10	NR_072994.2	n.3115C>T		non_coding_transcript_exon_variant	19/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R10	ENST00000376511.7	c.2624C>T	p.Pro875Leu	missense_variant	19/20	1	NM_002714.4	P1

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 25 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

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: 0.000309

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000132 AC: 25 AN: 189876 Hom.: 0 AF XY: 0.000148 AC XY: 15 AN XY: 101436

Gnomad AFR exome AF: 0.000140

Gnomad AMR exome AF: 0.0000758

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000120

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000171

Gnomad OTH exome AF: 0.000223

GnomAD4 exome AF: 0.000153 AC: 212 AN: 1384088 Hom.: 0 Cov.: 32 AF XY: 0.000137 AC XY: 93 AN XY: 678830

Gnomad4 AFR exome AF: 0.0000955

Gnomad4 AMR exome AF: 0.0000840

Gnomad4 ASJ exome AF: 0.0000475

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.000188

Gnomad4 FIN exome AF: 0.0000203

Gnomad4 NFE exome AF: 0.000172

Gnomad4 OTH exome AF: 0.0000878

GnomAD4 genome AF: 0.000164 AC: 25 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74430

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000396 Hom.: 0

Bravo AF: 0.000185

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.000332 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000129 AC: 15

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2022

The c.2624C>T (p.P875L) 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 2624, causing the proline (P) at amino acid position 875 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	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.46
Cadd	Uncertain	23
Dann	Benign	0.95
DEOGEN2	Benign	0.070	T
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.0068
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.033	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.58	D
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.25	N
REVEL	Benign	0.033
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.68	T
Polyphen		0.90	P
Vest4		0.29
MVP		0.22
MPC		0.38
ClinPred		0.047	T
GERP RS		3.5
Varity_R		0.088
gMVP		0.30

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

Other links and lift over

dbSNP: rs1052945; hg19: chr6-30569802; COSMIC: COSV64738610; COSMIC: COSV64738610;