Variant X-49269958-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033215.5(PPP1R3F):c.89C>T(p.Ala30Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 904,949 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000090 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.0000013 ( 0 hom. 1 hem. )

Consequence

PPP1R3F
NM_033215.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.497

Variant links:

Genes affected

PPP1R3F (HGNC:14944): (protein phosphatase 1 regulatory subunit 3F) This gene encodes a protein that has been identified as one of several type-1 protein phosphatase (PP1) regulatory subunits. One or two of these subunits, together with the well-conserved catalytic subunit, can form the PP1 holoenzyme, where the regulatory subunit functions to regulate substrate specificity and/or targeting to a particular cellular compartment. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2010]

PPP1R3F links:

ENSG00000290184 (HGNC:):

ENSG00000290184 links:

ENSG00000286181 (HGNC:53589): (FOXP3 regulating long intergenic non-coding RNA)

ENSG00000286181 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.112175554).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3F	NM_033215.5 link	c.89C>T	p.Ala30Val	missense_variant	1/4	ENST00000055335.11	NP_149992.3	Q6ZSY5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R3F	ENST00000055335.11 link	c.89C>T	p.Ala30Val	missense_variant	1/4	2	NM_033215.5	ENSP00000055335.6		Q6ZSY5-1
ENSG00000290184	ENST00000703450.1 link	c.-224+254G>A		intron_variant				ENSP00000515301.1		A0A494C1K1

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111518

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34586

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000190

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000126

AC:

AN:

793431

Hom.:

Cov.:

AF XY:

0.00000407

AC XY:

AN XY:

245711

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000111

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

AF:

0.00000897

AC:

AN:

111518

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34586

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000190

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

The c.89C>T (p.A30V) alteration is located in exon 1 (coding exon 1) of the PPP1R3F gene. This alteration results from a C to T substitution at nucleotide position 89, causing the alanine (A) at amino acid position 30 to be replaced by a valine (V). 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

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.82

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0021

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.58

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.26

REVEL

Benign

0.022

Sift

Benign

0.37

Sift4G

Pathogenic

0.0

Polyphen

0.033

Vest4

0.060

MutPred

0.33

Gain of sheet (P = 0.0028);

MVP

0.61

MPC

0.32

ClinPred

0.17

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.040

gMVP

0.10

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