NM_006246.5:c.362G>T

Variant names:

• chr14-63422087-C-A
• NM_006246.5:c.362G>T

Variant summary

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

The NM_006246.5(PPP2R5E):​c.362G>T​(p.Cys121Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP2R5E NM_006246.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.79

Genes affected

PPP2R5E (HGNC:9313): (protein phosphatase 2 regulatory subunit B'epsilon) The protein encoded by this gene belongs to the phosphatase 2A regulatory subunit B family. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes an epsilon isoform of the regulatory subunit B56 subfamily. Multiple transcript variants encoding several different isoforms have been found for this gene. [provided by RefSeq, Aug 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP2R5E	NM_006246.5	c.362G>T	p.Cys121Phe	missense_variant	Exon 4 of 14	ENST00000337537.8	NP_006237.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP2R5E	ENST00000337537.8	c.362G>T	p.Cys121Phe	missense_variant	Exon 4 of 14	1	NM_006246.5	ENSP00000337641.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.362G>T (p.C121F) alteration is located in exon 4 (coding exon 3) of the PPP2R5E gene. This alteration results from a G to T substitution at nucleotide position 362, causing the cysteine (C) at amino acid position 121 to be replaced by a phenylalanine (F). 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	0.11
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	23
DANN	Benign	0.96
DEOGEN2	Uncertain	0.61	D;.;.
Eigen	Benign	0.030
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.0035	T
MetaRNN	Uncertain	0.44	T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	L;.;L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.095
Sift	Benign	0.084	T;T;T
Sift4G	Uncertain	0.036	D;D;D
Polyphen		0.019	B;.;.
Vest4		0.60
MutPred		0.35		Gain of catalytic residue at C121 (P = 0.015);.;Gain of catalytic residue at C121 (P = 0.015);
MVP		0.14
MPC		1.9
ClinPred		0.82	D
GERP RS		5.4
Varity_R		0.30
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr14-63888805;