NM_006246.5:c.158-1069C>A

Variant names:

• chr14-63454954-G-T
• rs3783741
• NM_006246.5:c.158-1069C>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.158-1069C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,094 control chromosomes in the GnomAD database, including 11,184 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 (11184 hom., cov: 33)
• Consequence: PPP2R5E NM_006246.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.228
• Publications: 2 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=-0.98).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	NM_006246.5	MANE Select	c.158-1069C>A		intron	N/A	NP_006237.1
	PPP2R5E	NM_001282179.3		c.158-1069C>A		intron	N/A	NP_001269108.1
	PPP2R5E	NM_001282180.3		c.158-1069C>A		intron	N/A	NP_001269109.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP2R5E	ENST00000337537.8	TSL:1 MANE Select	c.158-1069C>A		intron	N/A	ENSP00000337641.3
	PPP2R5E	ENST00000555899.1	TSL:1	c.158-1069C>A		intron	N/A	ENSP00000452396.1
	PPP2R5E	ENST00000553266.5	TSL:1	n.741-32860C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50353 AN: 151976 Hom.: 11145 Cov.: 33

Gnomad AFR AF: 0.631

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.231

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: 0.332 AC: 50440 AN: 152094 Hom.: 11184 Cov.: 33 AF XY: 0.329 AC XY: 24480 AN XY: 74358

African (AFR) AF: 0.632 AC: 26200 AN: 41468

American (AMR) AF: 0.208 AC: 3180 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 753 AN: 3468

East Asian (EAS) AF: 0.426 AC: 2201 AN: 5164

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4818

European-Finnish (FIN) AF: 0.231 AC: 2444 AN: 10578

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

European-Non Finnish (NFE) AF: 0.203 AC: 13820 AN: 67984

Other (OTH) AF: 0.316 AC: 667 AN: 2114

Alfa AF: 0.240 Hom.: 2808

Bravo AF: 0.342

Asia WGS AF: 0.359 AC: 1245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.2
DANN	Benign	0.36
PhyloP100		0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3783741; hg19: chr14-63921672;