NM_014906.5:c.400C>A

Variant names:

• chr17-58756397-C-A
• rs1052458788
• NM_014906.5:c.400C>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_014906.5(PPM1E):​c.400C>A​(p.Arg134Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 1,210,214 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000066 (0 hom.)
• Consequence: PPM1E NM_014906.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13845512).
• BS2: High AC in GnomAdExome4 at 8 AD gene.

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.400C>A	p.Arg134Ser	missense	Exon 1 of 7	NP_055721.3
	PPM1E	NR_048561.1		n.529C>A		non_coding_transcript_exon	Exon 1 of 6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPM1E	ENST00000308249.4	TSL:1 MANE Select	c.400C>A	p.Arg134Ser	missense	Exon 1 of 7	ENSP00000312411.2	Q8WY54-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000661 AC: 8 AN: 1210214 Hom.: 0 Cov.: 33 AF XY: 0.00000680 AC XY: 4 AN XY: 587974

African (AFR) AF: 0.0000423 AC: 1 AN: 23630

American (AMR) AF: 0.00 AC: 0 AN: 10084

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16238

East Asian (EAS) AF: 0.00 AC: 0 AN: 27516

South Asian (SAS) AF: 0.00 AC: 0 AN: 44742

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3390

European-Non Finnish (NFE) AF: 0.00000705 AC: 7 AN: 992888

Other (OTH) AF: 0.00 AC: 0 AN: 49196

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.56
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
PhyloP100		2.0
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	0.020	N
REVEL	Benign	0.090
Sift	Benign	0.068	T
Sift4G	Benign	0.72	T
Vest4		0.40
MutPred		0.31		Gain of phosphorylation at R134 (P = 0.0096)
MVP		0.043
MPC		1.6
ClinPred		0.42	T
GERP RS		1.4
Varity_R		0.14
gMVP		0.15
Mutation Taster		=86/14	polymorphism

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: rs1052458788; hg19: chr17-56833758;