7-31692470-T-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006658.5(PPP1R17):c.29T>G(p.Leu10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 1,611,986 control chromosomes in the GnomAD database, including 387 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.018 ( 42 hom., cov: 33)

Exomes 𝑓: 0.015 ( 345 hom. )

Consequence

PPP1R17
NM_006658.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.12

Variant links:

Genes affected

PPP1R17 (HGNC:16973): (protein phosphatase 1 regulatory subunit 17) The protein encoded by this gene is found primarily in cerebellar Purkinje cells, where it functions as a protein phosphatase inhibitor. The encoded protein is a substrate for cGMP-dependent protein kinase. An allele of this gene was discovered that increases susceptibility to hypercholesterolemia. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2010]

PPP1R17 links:

PDE1C (HGNC:8776): (phosphodiesterase 1C) This gene encodes an enzyme that belongs to the 3'5'-cyclic nucleotide phosphodiesterase family. Members of this family catalyze hydrolysis of the cyclic nucleotides, cyclic adenosine monophosphate and cyclic guanosine monophosphate, to the corresponding nucleoside 5'-monophosphates. The enzyme encoded by this gene regulates proliferation and migration of vascular smooth muscle cells, and neointimal hyperplasia. This enzyme also plays a role in pathological vascular remodeling by regulating the stability of growth factor receptors, such as PDGF-receptor-beta. [provided by RefSeq, Jul 2016]

PDE1C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019840598).

BP6

Variant 7-31692470-T-G is Benign according to our data. Variant chr7-31692470-T-G is described in ClinVar as [Benign]. Clinvar id is 403336.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-31692470-T-G is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R17	NM_006658.5 link	c.29T>G	p.Leu10Arg	missense_variant	Exon 2 of 5	ENST00000342032.8	NP_006649.2	O96001-1A0A090N8N7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R17	ENST00000342032.8 link	c.29T>G	p.Leu10Arg	missense_variant	Exon 2 of 5	1	NM_006658.5	ENSP00000340125.3		O96001-1
PPP1R17	ENST00000409146.3 link	c.29T>G	p.Leu10Arg	missense_variant	Exon 2 of 4	2		ENSP00000386459.3		O96001-2

Frequencies

GnomAD3 genomes

AF:

0.0182

AC:

2768

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.0499

Gnomad EAS

AF:

0.00694

Gnomad SAS

AF:

0.0543

Gnomad FIN

AF:

0.00678

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0198

AC:

4973

AN:

251416

Hom.:

105

AF XY:

0.0217

AC XY:

2953

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.0287

Gnomad AMR exome

AF:

0.0105

Gnomad ASJ exome

AF:

0.0566

Gnomad EAS exome

AF:

0.00653

Gnomad SAS exome

AF:

0.0589

Gnomad FIN exome

AF:

0.00559

Gnomad NFE exome

AF:

0.0121

Gnomad OTH exome

AF:

0.0257

GnomAD4 exome

AF:

0.0148

AC:

21554

AN:

1459710

Hom.:

345

Cov.:

AF XY:

0.0162

AC XY:

11768

AN XY:

726316

show subpopulations

Gnomad4 AFR exome

AF:

0.0308

Gnomad4 AMR exome

AF:

0.0117

Gnomad4 ASJ exome

AF:

0.0543

Gnomad4 EAS exome

AF:

0.00383

Gnomad4 SAS exome

AF:

0.0581

Gnomad4 FIN exome

AF:

0.00625

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.0194

GnomAD4 genome

AF:

0.0182

AC:

2774

AN:

152276

Hom.:

Cov.:

AF XY:

0.0185

AC XY:

1375

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0289

Gnomad4 AMR

AF:

0.0136

Gnomad4 ASJ

AF:

0.0499

Gnomad4 EAS

AF:

0.00696

Gnomad4 SAS

AF:

0.0554

Gnomad4 FIN

AF:

0.00678

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.0218

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.0187

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.0261

AC:

115

ESP6500EA

AF:

0.0136

AC:

117

ExAC

AF:

0.0202

AC:

2453

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

EpiCase

AF:

0.0147

EpiControl

AF:

0.0152

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;.

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.62

T;T

MetaRNN

Benign

0.0020

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;L

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.023

Sift

Benign

0.17

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.010

B;.

Vest4

0.090

MPC

0.27

ClinPred

0.0030

GERP RS

2.4

Varity_R

0.10

gMVP

0.27

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