NM_006246.5:c.158-19479C>A

Variant names:

• chr14-63473364-G-T
• rs1012145
• NM_006246.5:c.158-19479C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006246.5(PPP2R5E):​c.158-19479C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 151,964 control chromosomes in the GnomAD database, including 11,064 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (11064 hom., cov: 32)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53
• Publications: 5 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

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.158-19479C>A		intron	N/A	NP_006237.1	Q16537-1
	PPP2R5E	NM_001282179.3		c.158-19479C>A		intron	N/A	NP_001269108.1	Q16537-1
	PPP2R5E	NM_001282180.3		c.158-19479C>A		intron	N/A	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.158-19479C>A		intron	N/A	ENSP00000337641.3	Q16537-1
	PPP2R5E	ENST00000555899.1	TSL:1	c.158-19479C>A		intron	N/A	ENSP00000452396.1	Q16537-2
	PPP2R5E	ENST00000553266.5	TSL:1	n.741-51270C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50048 AN: 151846 Hom.: 11024 Cov.: 32

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.314

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.330 AC: 50137 AN: 151964 Hom.: 11064 Cov.: 32 AF XY: 0.327 AC XY: 24299 AN XY: 74280

African (AFR) AF: 0.632 AC: 26167 AN: 41410

American (AMR) AF: 0.208 AC: 3172 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3470

East Asian (EAS) AF: 0.385 AC: 1989 AN: 5164

South Asian (SAS) AF: 0.206 AC: 992 AN: 4818

European-Finnish (FIN) AF: 0.230 AC: 2433 AN: 10556

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13801 AN: 67968

Other (OTH) AF: 0.316 AC: 667 AN: 2108

Alfa AF: 0.247 Hom.: 17898

Bravo AF: 0.340

Asia WGS AF: 0.351 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.15
DANN	Benign	0.37
PhyloP100		-1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs1012145; hg19: chr14-63940082;