X-49270143-G-A

Position:

• chrX-49270143-G-A

Variant summary

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

The NM_033215.5(PPP1R3F):​c.274G>A​(p.Glu92Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000104 in 960,619 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000010 (0 hom. 1 hem.)
• Consequence: PPP1R3F NM_033215.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.72

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]

(HGNC:):

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=0.21778396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP1R3F	NM_033215.5	c.274G>A	p.Glu92Lys	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.274G>A	p.Glu92Lys	missense_variant	1/4	2	NM_033215.5	ENSP00000055335	P1
PPP1R3F	ENST00000495799.5	c.-32+210G>A		intron_variant		1		ENSP00000417535
	ENST00000651462.1	n.310+69C>T		intron_variant, non_coding_transcript_variant
PPP1R3F	ENST00000466508.5	c.-298+210G>A		intron_variant		2		ENSP00000420687

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome AF: 0.00000104 AC: 1 AN: 960619 Hom.: 0 Cov.: 30 AF XY: 0.00000333 AC XY: 1 AN XY: 300089

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000443

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 Cov.: 24

Bravo AF: 0.0000113

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

Sep 15, 2021

The c.274G>A (p.E92K) 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 274, causing the glutamic acid (E) at amino acid position 92 to be replaced by a lysine (K). 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	0.16
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.096	T
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.61	T
M_CAP	Pathogenic	0.84	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.34	N
MutationTaster	Benign	1.0	D;D;D;N
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.036
Sift	Benign	0.21	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.15
MutPred		0.26		Gain of ubiquitination at E92 (P = 0.006);
MVP		0.54
MPC		1.1
ClinPred		0.67	D
GERP RS		2.7
Varity_R		0.16
gMVP		0.27

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: rs1451247246; hg19: chrX-49126606;