chr7-31692491-T-C

Position:

• chr7-31692491-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006658.5(PPP1R17):​c.50T>C​(p.Leu17Pro) variant causes a missense change. 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP1R17 NM_006658.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.86

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3538646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP1R17	NM_006658.5	c.50T>C	p.Leu17Pro	missense_variant	2/5	ENST00000342032.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP1R17	ENST00000342032.8	c.50T>C	p.Leu17Pro	missense_variant	2/5	1	NM_006658.5	P1
PPP1R17	ENST00000409146.3	c.50T>C	p.Leu17Pro	missense_variant	2/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1459144 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726150

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: 0.00

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

May 17, 2023

The c.50T>C (p.L17P) alteration is located in exon 2 (coding exon 1) of the PPP1R17 gene. This alteration results from a T to C substitution at nucleotide position 50, causing the leucine (L) at amino acid position 17 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	0.17
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.65	T;T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.2	M;M
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.99	D;.
Vest4		0.60
MutPred		0.30		Loss of stability (P = 0.0012);Loss of stability (P = 0.0012);
MVP		0.33
MPC		0.44
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.81
gMVP		0.52

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: chr7-31732105;