X-49270476-C-G

Position:

• chrX-49270476-C-G

Variant summary

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

The NM_033215.5(PPP1R3F):​c.607C>G​(p.Pro203Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 25)
• Consequence: PPP1R3F NM_033215.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.28

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]

ENSG00000290184 (HGNC:):

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

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=0.089144886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3F	NM_033215.5	c.607C>G	p.Pro203Ala	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	c.607C>G	p.Pro203Ala	missense_variant	1/4	2	NM_033215.5	ENSP00000055335.6
ENSG00000290184	ENST00000703450.1	c.-488G>C		5_prime_UTR_variant	1/4			ENSP00000515301.1

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 27, 2024

The c.607C>G (p.P203A) alteration is located in exon 1 (coding exon 1) of the PPP1R3F gene. This alteration results from a C to G substitution at nucleotide position 607, causing the proline (P) at amino acid position 203 to be replaced by an alanine (A). 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	0.069
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	19
DANN	Benign	0.81
DEOGEN2	Benign	0.0040	T
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	0.96	N
REVEL	Benign	0.038
Sift	Benign	0.70	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.47		Loss of glycosylation at P203 (P = 0.0214);
MVP		0.65
MPC		0.89
ClinPred		0.054	T
GERP RS		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.045
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-49126939;