17-39635843-C-A

Position:

• chr17-39635843-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM1 BP4_Strong BP6_Very_Strong BS2

The NM_032192.4(PPP1R1B):​c.593C>A​(p.Ser198Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,446 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (6 hom., cov: 32)
  • Exomes 𝑓: 0.011 (118 hom.)
• Consequence: PPP1R1B NM_032192.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0750

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]

LOC124903998 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• PM1: In a modified_residue Phosphoserine (size 0) in uniprot entity PPR1B_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.003179282).
• BP6: Variant 17-39635843-C-A is Benign according to our data. Variant chr17-39635843-C-A is described in ClinVar as [Benign]. Clinvar id is 775160.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R1B	NM_032192.4	c.593C>A	p.Ser198Tyr	missense_variant	7/7	ENST00000254079.9	NP_115568.2
LOC124903998	XR_007065749.1	n.301-817G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R1B	ENST00000254079.9	c.593C>A	p.Ser198Tyr	missense_variant	7/7	1	NM_032192.4	ENSP00000254079	P1

Frequencies

GnomAD3 genomes AF: 0.00674 AC: 1025 AN: 152176 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00179

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00497

Gnomad ASJ AF: 0.0138

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00186

Gnomad FIN AF: 0.00678

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0107

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00731 AC: 1833 AN: 250802 Hom.: 11 AF XY: 0.00755 AC XY: 1024 AN XY: 135598

Gnomad AFR exome AF: 0.00173

Gnomad AMR exome AF: 0.00318

Gnomad ASJ exome AF: 0.0156

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00160

Gnomad FIN exome AF: 0.00661

Gnomad NFE exome AF: 0.0114

Gnomad OTH exome AF: 0.00850

GnomAD4 exome AF: 0.0106 AC: 15435 AN: 1461152 Hom.: 118 Cov.: 31 AF XY: 0.0103 AC XY: 7504 AN XY: 726836

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00338

Gnomad4 ASJ exome AF: 0.0148

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00219

Gnomad4 FIN exome AF: 0.00630

Gnomad4 NFE exome AF: 0.0123

Gnomad4 OTH exome AF: 0.00983

GnomAD4 genome AF: 0.00672 AC: 1024 AN: 152294 Hom.: 6 Cov.: 32 AF XY: 0.00645 AC XY: 480 AN XY: 74458

Gnomad4 AFR AF: 0.00178

Gnomad4 AMR AF: 0.00497

Gnomad4 ASJ AF: 0.0138

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00678

Gnomad4 NFE AF: 0.0107

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00938 Hom.: 18

Bravo AF: 0.00660

TwinsUK AF: 0.0173 AC: 64

ALSPAC AF: 0.0109 AC: 42

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.0109 AC: 94

ExAC AF: 0.00711 AC: 863

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0105

EpiControl AF: 0.0119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.21	T;T;.;.;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.74	.;T;T;.;T
MetaRNN	Benign	0.0032	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-1.1	.;N;.;N;N
REVEL	Benign	0.020
Sift	Uncertain	0.014	.;D;.;D;D
Sift4G	Benign	0.081	T;T;T;D;D
Polyphen		0.14	B;B;.;.;.
Vest4		0.25
MVP		0.12
MPC		0.55
ClinPred		0.0016	T
GERP RS		-3.1
Varity_R		0.057
gMVP		0.026

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: rs79497069; hg19: chr17-37792096;