X-49270329-G-A

Position:

• chrX-49270329-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_033215.5(PPP1R3F):​c.460G>A​(p.Val154Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000293 in 1,023,165 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000029 (0 hom. 0 hem.)
• Consequence: PPP1R3F NM_033215.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.96

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3581512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3F	NM_033215.5	c.460G>A	p.Val154Met	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.460G>A	p.Val154Met	missense_variant	1/4	2	NM_033215.5	ENSP00000055335.6
ENSG00000290184	ENST00000703450.1	c.-341C>T		5_prime_UTR_variant	1/4			ENSP00000515301.1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000293 AC: 3 AN: 1023165 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 329039

Gnomad4 AFR exome AF: 0.0000855

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: 0.00000123

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000378

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

Mar 19, 2024

The c.460G>A (p.V154M) 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 460, causing the valine (V) at amino acid position 154 to be replaced by a methionine (M). 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	0.22
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0095	T
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.55	T
M_CAP	Pathogenic	0.60	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	0.0	N
REVEL	Benign	0.086
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.62	P
Vest4		0.27
MutPred		0.67		Loss of sheet (P = 0.0357);
MVP		0.47
MPC		1.1
ClinPred		0.48	T
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.11
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

Other links and lift over

dbSNP: rs1250720100; hg19: chrX-49126792;