NM_014906.5:c.464+14123C>T

Variant names:

• chr17-58770584-C-T
• rs9303401
• NM_014906.5:c.464+14123C>T

Variant summary

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

The NM_014906.5(PPM1E):​c.464+14123C>T 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 151,880 control chromosomes in the GnomAD database, including 8,890 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 (8890 hom., cov: 32)
• Consequence: PPM1E NM_014906.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120
• Publications: 32 publications found

Genes affected

PPM1E (HGNC:19322): (protein phosphatase, Mg2+/Mn2+ dependent 1E) This gene encodes a member of the PPM family of serine/threonine-protein phosphatases. The encoded protein is localized to the nucleus and dephosphorylates and inactivates multiple substrates including serine/threonine-protein kinase PAK 1, 5'-AMP-activated protein kinase (AMPK) and the multifunctional calcium/calmodulin-dependent protein kinases. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014906.5. 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
	PPM1E	NM_014906.5	MANE Select	c.464+14123C>T		intron	N/A	NP_055721.3
	PPM1E	NR_048561.1		n.593+14123C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1E	ENST00000308249.4	TSL:1 MANE Select	c.464+14123C>T		intron	N/A	ENSP00000312411.2	Q8WY54-2

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50339 AN: 151758 Hom.: 8873 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.360

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.286

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

GnomAD4 genome AF: 0.332 AC: 50397 AN: 151880 Hom.: 8890 Cov.: 32 AF XY: 0.337 AC XY: 25040 AN XY: 74234

African (AFR) AF: 0.430 AC: 17796 AN: 41422

American (AMR) AF: 0.251 AC: 3815 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.169 AC: 587 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2528 AN: 5166

South Asian (SAS) AF: 0.417 AC: 2012 AN: 4822

European-Finnish (FIN) AF: 0.360 AC: 3795 AN: 10532

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18866 AN: 67964

Other (OTH) AF: 0.294 AC: 621 AN: 2110

Alfa AF: 0.284 Hom.: 21385

Bravo AF: 0.319

Asia WGS AF: 0.462 AC: 1604 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	6.2
DANN	Benign	0.68
PhyloP100		0.012
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: rs9303401; hg19: chr17-56847945;