6-30603512-C-G

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2 BP4_Strong BP6_Moderate BS2

The NM_002714.4(PPP1R10):c.1727G>C(p.Gly576Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,613,134 control chromosomes in the GnomAD database, including 1 homozygotes. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (1 hom.)
• Consequence: PPP1R10 NM_002714.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.136

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 -9 ACMG points.

• PP2: Missense variant where missense usually causes diseases, PPP1R10
• BP4: Computational evidence support a benign effect (MetaRNN=0.022518575).
• BP6: Variant 6-30603512-C-G is Benign according to our data. Variant chr6-30603512-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2339105.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R10	NM_002714.4	c.1727G>C	p.Gly576Ala	missense_variant	16/20	ENST00000376511.7
PPP1R10	NM_001376195.1	c.1727G>C	p.Gly576Ala	missense_variant	16/20
PPP1R10	XM_011514722.2	c.1727G>C	p.Gly576Ala	missense_variant	17/21
PPP1R10	NR_072994.2	n.2218G>C		non_coding_transcript_exon_variant	16/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R10	ENST00000376511.7	c.1727G>C	p.Gly576Ala	missense_variant	16/20	1	NM_002714.4	P1

Frequencies

GnomAD3 genomes AF: 0.000388 AC: 59 AN: 152024 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.0000719 AC: 18 AN: 250206 Hom.: 0 AF XY: 0.0000739 AC XY: 10 AN XY: 135316

Gnomad AFR exome AF: 0.000925

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000328

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.0000726 AC: 106 AN: 1460992 Hom.: 1 Cov.: 32 AF XY: 0.0000647 AC XY: 47 AN XY: 726828

Gnomad4 AFR exome AF: 0.00209

Gnomad4 AMR exome AF: 0.0000449

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000929

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000270

Gnomad4 OTH exome AF: 0.000215

GnomAD4 genome AF: 0.000394 AC: 60 AN: 152142 Hom.: 0 Cov.: 32 AF XY: 0.000390 AC XY: 29 AN XY: 74394

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000475

Alfa AF: 0.0000397 Hom.: 0

Bravo AF: 0.000397

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 24, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	16
Dann	Benign	0.83
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	0.45	N
REVEL	Benign	0.079
Sift	Benign	0.069	T
Sift4G	Benign	0.64	T
Polyphen		0.0020	B
Vest4		0.33
MVP		0.33
MPC		0.41
ClinPred		0.012	T
GERP RS		4.0
Varity_R		0.059
gMVP		0.29

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: rs148152155; hg19: chr6-30571289;