7-31697032-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006658.5(PPP1R17):​c.303C>G​(p.Ile101Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

PPP1R17
NM_006658.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0680
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05633834).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP1R17NM_006658.5 linkc.303C>G p.Ile101Met missense_variant Exon 4 of 5 ENST00000342032.8 NP_006649.2 O96001-1A0A090N8N7

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP1R17ENST00000342032.8 linkc.303C>G p.Ile101Met missense_variant Exon 4 of 5 1 NM_006658.5 ENSP00000340125.3 O96001-1
PPP1R17ENST00000409146.3 linkc.150C>G p.Ile50Met missense_variant Exon 3 of 4 2 ENSP00000386459.3 O96001-2
PPP1R17ENST00000498609.1 linkn.184C>G non_coding_transcript_exon_variant Exon 2 of 4 4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152114
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251222
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135774
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461840
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152114
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 20, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.303C>G (p.I101M) alteration is located in exon 4 (coding exon 3) of the PPP1R17 gene. This alteration results from a C to G substitution at nucleotide position 303, causing the isoleucine (I) at amino acid position 101 to be replaced by a methionine (M). 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
0.081
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
13
DANN
Benign
0.94
DEOGEN2
Benign
0.058
T;.
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.65
T;T
M_CAP
Benign
0.0066
T
MetaRNN
Benign
0.056
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.34
N;.
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-0.22
N;N
REVEL
Benign
0.0080
Sift
Benign
0.070
T;D
Sift4G
Benign
0.099
T;T
Polyphen
0.19
B;.
Vest4
0.20
MutPred
0.27
Loss of sheet (P = 0.0126);.;
MVP
0.030
MPC
0.11
ClinPred
0.053
T
GERP RS
-0.65
Varity_R
0.059
gMVP
0.054

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.

Other links and lift over

dbSNP: rs1455071177; hg19: chr7-31736646; API