17-58955693-C-T

Variant names:

• chr17-58955693-C-T
• NM_014906.5:c.509C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014906.5(PPM1E):​c.509C>T​(p.Ser170Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: PPM1E NM_014906.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

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

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2948805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPM1E	NM_014906.5	c.509C>T	p.Ser170Leu	missense_variant	Exon 2 of 7	ENST00000308249.4	NP_055721.3
PPM1E	XM_047435630.1	c.-3C>T		5_prime_UTR_variant	Exon 2 of 6		XP_047291586.1
PPM1E	XM_024450657.2	c.-209C>T		5_prime_UTR_variant	Exon 2 of 7		XP_024306425.1
PPM1E	NR_048561.1	n.638C>T		non_coding_transcript_exon_variant	Exon 2 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPM1E	ENST00000308249.4	c.509C>T	p.Ser170Leu	missense_variant	Exon 2 of 7	1	NM_014906.5	ENSP00000312411.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.509C>T (p.S170L) alteration is located in exon 2 (coding exon 2) of the PPM1E gene. This alteration results from a C to T substitution at nucleotide position 509, causing the serine (S) at amino acid position 170 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	23
DANN	Uncertain	1.0
Eigen	Benign	0.015
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.16	N
REVEL	Benign	0.11
Sift	Benign	0.097	T
Sift4G	Benign	0.28	T
Vest4		0.63
MutPred		0.34		Loss of disorder (P = 0.0178);
MVP		0.068
MPC		1.2
ClinPred		0.62	D
GERP RS		5.2
Varity_R		0.13
gMVP		0.46

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-57033054;