NM_006246.5:c.481T>G

Variant names:

• chr14-63415208-A-C
• rs1313412531
• NM_006246.5:c.481T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006246.5(PPP2R5E):​c.481T>G​(p.Phe161Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,603,428 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: PPP2R5E NM_006246.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• Publications: 1 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006246.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	NM_006246.5	MANE Select	c.481T>G	p.Phe161Val	missense	Exon 5 of 14	NP_006237.1	Q16537-1
	PPP2R5E	NM_001282179.3		c.481T>G	p.Phe161Val	missense	Exon 5 of 14	NP_001269108.1	Q16537-1
	PPP2R5E	NM_001282180.3		c.481T>G	p.Phe161Val	missense	Exon 5 of 14	NP_001269109.1	Q16537-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	ENST00000337537.8	TSL:1 MANE Select	c.481T>G	p.Phe161Val	missense	Exon 5 of 14	ENSP00000337641.3	Q16537-1
	PPP2R5E	ENST00000555899.1	TSL:1	c.481T>G	p.Phe161Val	missense	Exon 5 of 14	ENSP00000452396.1	Q16537-2
	PPP2R5E	ENST00000553266.5	TSL:1	n.867T>G		non_coding_transcript_exon	Exon 4 of 12

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250294 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1451150 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 722540

African (AFR) AF: 0.00 AC: 0 AN: 33202

American (AMR) AF: 0.00 AC: 0 AN: 44502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25986

East Asian (EAS) AF: 0.00 AC: 0 AN: 39496

South Asian (SAS) AF: 0.00 AC: 0 AN: 85656

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53294

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1103244

Other (OTH) AF: 0.00 AC: 0 AN: 60030

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74470

African (AFR) AF: 0.0000722 AC: 3 AN: 41554

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.0000330 Hom.: 0

Bravo AF: 0.0000151

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Pathogenic	0.44	D
BayesDel_noAF	Pathogenic	0.39
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.76	D
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.67	D
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		9.3
PrimateAI	Pathogenic	0.89	D
PROVEAN	Pathogenic	-6.0	D
REVEL	Uncertain	0.60
Sift	Benign	0.036	D
Sift4G	Benign	0.098	T
Polyphen		0.19	B
Vest4		0.73
MVP		0.69
MPC		2.3
ClinPred		0.99	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.67
gMVP		0.71
Mutation Taster		=7/93	disease causing

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

Other links and lift over

dbSNP: rs1313412531; hg19: chr14-63881926;