17-39635654-C-A

Position:

• chr17-39635654-C-A

Variant summary

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

The NM_032192.4(PPP1R1B):​c.493C>A​(p.Arg165Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PPP1R1B NM_032192.4 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.37

Genes affected

PPP1R1B (HGNC:9287): (protein phosphatase 1 regulatory inhibitor subunit 1B) This gene encodes a bifunctional signal transduction molecule. Dopaminergic and glutamatergic receptor stimulation regulates its phosphorylation and function as a kinase or phosphatase inhibitor. As a target for dopamine, this gene may serve as a therapeutic target for neurologic and psychiatric disorders. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

PPP1R1B (HGNC:):

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=0.2590616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R1B	NM_032192.4	c.493C>A	p.Arg165Ser	missense_variant	6/7	ENST00000254079.9	NP_115568.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R1B	ENST00000254079.9	c.493C>A	p.Arg165Ser	missense_variant	6/7	1	NM_032192.4	ENSP00000254079.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727224

Gnomad4 AFR exome AF: 0.0000299

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

Bravo AF: 0.00000378

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Psychiatry Genetics Yale University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Benign	-0.0026	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T;T;.;.;.
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.60
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Benign	0.84	.;T;T;.;T
M_CAP	Benign	0.025	D
MetaRNN	Benign	0.26	T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	M;M;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.1	.;N;.;N;N
REVEL	Benign	0.11
Sift	Pathogenic	0.0	.;D;.;D;D
Sift4G	Uncertain	0.033	D;D;D;T;T
Polyphen		1.0	D;D;.;.;.
Vest4		0.43
MutPred		0.32		Gain of phosphorylation at R165 (P = 0.0066);Gain of phosphorylation at R165 (P = 0.0066);.;.;.;
MVP		0.27
MPC		1.3
ClinPred		0.99	D
GERP RS		5.3
Varity_R		0.37
gMVP		0.070

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

Other links and lift over

dbSNP: rs367543181; hg19: chr17-37791907;