NM_014906.5:c.400C>T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014906.5(PPM1E):​c.400C>T​(p.Arg134Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R134S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPM1E NM_014906.5 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21763507).

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>T	p.Arg134Cys	missense	Exon 1 of 7	NP_055721.3
	PPM1E	NR_048561.1		n.529C>T		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>T	p.Arg134Cys	missense	Exon 1 of 7	ENSP00000312411.2	Q8WY54-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1210214 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 587974

African (AFR) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 992888

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-0.049
Eigen_PC	Benign	-0.057
FATHMM_MKL	Benign	0.35	N
LIST_S2	Benign	0.69	T
M_CAP	Pathogenic	0.45	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.99	T
PhyloP100		2.0
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.11
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.048	D
Vest4		0.41
MutPred		0.25		Gain of glycosylation at S132 (P = 0.0591)
MVP		0.043
MPC		2.4
ClinPred		0.69	D
GERP RS		1.4
Varity_R		0.16
gMVP		0.18

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;