20-59939636-T-C

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_006242.4(PPP1R3D):c.296A>G(p.Gln99Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000232 in 1,420,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

PPP1R3D
NM_006242.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.06

Variant links:

Genes affected

PPP1R3D (HGNC:9294): (protein phosphatase 1 regulatory subunit 3D) Phosphorylation of serine and threonine residues in proteins is a crucial step in the regulation of many cellular functions ranging from hormonal regulation to cell division and even short-term memory. The level of phosphorylation is controlled by the opposing actions of protein kinases and protein phosphatases. Protein phosphatase 1 (PP1) is 1 of 4 major serine/threonine-specific protein phosphatases which have been identified in eukaryotic cells. PP1 associates with various regulatory subunits that dictate its subcellular localization and modulate its substrate specificity. Several subunits that target PP1 to glycogen have been identified. This gene encodes a glycogen-targeting subunit of PP1. [provided by RefSeq, Jul 2008]

PPP1R3D links:

FAM217B (HGNC:16170): (family with sequence similarity 217 member B) Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

FAM217B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03842807).

BP6

Variant 20-59939636-T-C is Benign according to our data. Variant chr20-59939636-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3782612.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3D	NM_006242.4 link	c.296A>G	p.Gln99Arg	missense_variant	Exon 1 of 1	ENST00000370996.5	NP_006233.1	O95685Q86X09
FAM217B	NM_001190826.2 link	c.-203+1524T>C		intron_variant	Intron 2 of 4		NP_001177755.1	Q9NTX9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R3D	ENST00000370996.5 link	c.296A>G	p.Gln99Arg	missense_variant	Exon 1 of 1	6	NM_006242.4	ENSP00000360035.3		O95685
FAM217B	ENST00000358293.7 link	c.-203+1524T>C		intron_variant	Intron 2 of 4	2		ENSP00000351040.3		Q9NTX9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000108

AC:

AN:

184836

Hom.:

AF XY:

0.0000193

AC XY:

AN XY:

103634

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000232

AC:

AN:

1420986

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

704600

show subpopulations

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:

0.0000237

Gnomad4 OTH exome

AF:

0.000119

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Dec 21, 2024

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.57

DEOGEN2

Benign

0.0042

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.24

M_CAP

Benign

0.033

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.9

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

1.4

REVEL

Benign

0.086

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.031

MutPred

0.25

Gain of MoRF binding (P = 0.0241);

MVP

0.31

MPC

0.87

ClinPred

0.015

GERP RS

3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.052

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over