rs36047130

Variant names:

• chr7-31692470-T-G
• rs36047130
• NM_006658.5:c.29T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-31692470-T-G
• chr7-31692470-T-A
• chr7-31692470-T-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (42 hom., cov: 33)
  • Exomes 𝑓: 0.015 (345 hom.)
• Consequence: PPP1R17 NM_006658.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.12
• Publications: 9 publications found

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]

PDE1C Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• hearing loss, autosomal dominant 74

  Inheritance: AD, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 403336.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0645 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006658.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R17	NM_006658.5	MANE Select	c.29T>G	p.Leu10Arg	missense	Exon 2 of 5	NP_006649.2	O96001-1
	PPP1R17	NM_001145123.3		c.29T>G	p.Leu10Arg	missense	Exon 2 of 4	NP_001138595.1	O96001-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP1R17	ENST00000342032.8	TSL:1 MANE Select	c.29T>G	p.Leu10Arg	missense	Exon 2 of 5	ENSP00000340125.3	O96001-1
	PPP1R17	ENST00000409146.3	TSL:2	c.29T>G	p.Leu10Arg	missense	Exon 2 of 4	ENSP00000386459.3	O96001-2
	PPP1R17	ENST00000927588.1		c.29T>G	p.Leu10Arg	missense	Exon 2 of 4	ENSP00000597647.1

Frequencies

GnomAD3 genomes AF: 0.0182 AC: 2768 AN: 152158 Hom.: 42 Cov.: 33

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

GnomAD2 exomes AF: 0.0198 AC: 4973 AN: 251416 AF XY: 0.0217

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 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.: 29 AF XY: 0.0162 AC XY: 11768 AN XY: 726316

African (AFR) AF: 0.0308 AC: 1028 AN: 33410

American (AMR) AF: 0.0117 AC: 523 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0543 AC: 1418 AN: 26120

East Asian (EAS) AF: 0.00383 AC: 152 AN: 39662

South Asian (SAS) AF: 0.0581 AC: 5007 AN: 86174

European-Finnish (FIN) AF: 0.00625 AC: 334 AN: 53418

Middle Eastern (MID) AF: 0.0701 AC: 404 AN: 5762

European-Non Finnish (NFE) AF: 0.0104 AC: 11516 AN: 1110116

Other (OTH) AF: 0.0194 AC: 1172 AN: 60332

GnomAD4 genome AF: 0.0182 AC: 2774 AN: 152276 Hom.: 42 Cov.: 33 AF XY: 0.0185 AC XY: 1375 AN XY: 74454

African (AFR) AF: 0.0289 AC: 1203 AN: 41576

American (AMR) AF: 0.0136 AC: 208 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0499 AC: 173 AN: 3468

East Asian (EAS) AF: 0.00696 AC: 36 AN: 5176

South Asian (SAS) AF: 0.0554 AC: 267 AN: 4820

European-Finnish (FIN) AF: 0.00678 AC: 72 AN: 10614

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0111 AC: 755 AN: 68000

Other (OTH) AF: 0.0218 AC: 46 AN: 2114

Alfa AF: 0.0145 Hom.: 83

Bravo AF: 0.0187

TwinsUK AF: 0.0116 AC: 43

ALSPAC AF: 0.0104 AC: 40

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

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.081
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.31	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.49	N
LIST_S2	Benign	0.62	T
MetaRNN	Benign	0.0020	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.1
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.023
Sift	Benign	0.17	T
Sift4G	Benign	0.18	T
Polyphen		0.010	B
Vest4		0.090
MPC		0.27
ClinPred		0.0030	T
GERP RS		2.4
Varity_R		0.10
gMVP		0.27
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs36047130; hg19: chr7-31732084; COSMIC: COSV107405045; COSMIC: COSV107405045;