Variant X-49269927-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_033215.5(PPP1R3F):c.58G>A(p.Ala20Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000773 in 905,850 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.000045 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.0000025 ( 0 hom. 1 hem. )

Consequence

PPP1R3F
NM_033215.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.938

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13369629).

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3F	NM_033215.5 linkuse as main transcript	c.58G>A	p.Ala20Thr	missense_variant	1/4	ENST00000055335.11	NP_149992.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP1R3F	ENST00000055335.11 linkuse as main transcript	c.58G>A	p.Ala20Thr	missense_variant	1/4	2	NM_033215.5	ENSP00000055335	P1	Q6ZSY5-1
PPP1R3F	ENST00000495799.5 linkuse as main transcript	c.-38G>A		5_prime_UTR_variant	1/4	1		ENSP00000417535		Q6ZSY5-2
	ENST00000651462.1 linkuse as main transcript	n.310+285C>T		intron_variant, non_coding_transcript_variant
PPP1R3F	ENST00000466508.5 linkuse as main transcript	c.-304G>A		5_prime_UTR_variant	1/5	2		ENSP00000420687		Q6ZSY5-2

Frequencies

GnomAD3 genomes

AF:

0.0000448

AC:

AN:

111641

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

34559

show subpopulations

Gnomad AFR

AF:

0.000161

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000252

AC:

AN:

794209

Hom.:

Cov.:

AF XY:

0.00000406

AC XY:

AN XY:

246333

show subpopulations

Gnomad4 AFR exome

AF:

0.0000605

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:

0.00000146

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000448

AC:

AN:

111641

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

34559

show subpopulations

Gnomad4 AFR

AF:

0.000161

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

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

Jun 22, 2021

The c.58G>A (p.A20T) alteration is located in exon 1 (coding exon 1) of the PPP1R3F gene. This alteration results from a G to A substitution at nucleotide position 58, causing the alanine (A) at amino acid position 20 to be replaced by a threonine (T). 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

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0013

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

D;D;D;N

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-0.010

REVEL

Benign

0.053

Sift

Benign

0.076

Sift4G

Pathogenic

0.0

Polyphen

0.26

Vest4

0.14

MutPred

0.15

Gain of glycosylation at A20 (P = 0.0027);

MVP

0.44

MPC

1.0

ClinPred

0.41

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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