7-31707216-T-C

Position:

• chr7-31707216-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006658.5(PPP1R17):​c.401T>C​(p.Leu134Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP1R17 NM_006658.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

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]

ACMG classification

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=0.21496308).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R17	NM_006658.5	c.401T>C	p.Leu134Pro	missense_variant	5/5	ENST00000342032.8	NP_006649.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R17	ENST00000342032.8	c.401T>C	p.Leu134Pro	missense_variant	5/5	1	NM_006658.5	ENSP00000340125.3
PPP1R17	ENST00000409146.3	c.248T>C	p.Leu83Pro	missense_variant	4/4	2		ENSP00000386459.3
PPP1R17	ENST00000498609.1	n.282T>C		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

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

Oct 25, 2023

The c.401T>C (p.L134P) alteration is located in exon 5 (coding exon 4) of the PPP1R17 gene. This alteration results from a T to C substitution at nucleotide position 401, causing the leucine (L) at amino acid position 134 to be replaced by a proline (P). 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	0.24
BayesDel_addAF	Uncertain	0.039	T
BayesDel_noAF	Benign	-0.18
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.31	T;.
Eigen	Benign	0.014
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.21	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Uncertain	-3.3	D;D
REVEL	Benign	0.14
Sift	Benign	0.091	T;T
Sift4G	Benign	0.093	T;T
Polyphen		0.0060	B;.
Vest4		0.45
MutPred		0.44		Gain of relative solvent accessibility (P = 0.0023);.;
MVP		0.29
MPC		0.43
ClinPred		0.96	D
GERP RS		4.7
Varity_R		0.76
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-31746830;