11-74171448-C-A

Position:

• chr11-74171448-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016147.3(PPME1):​c.27C>A​(p.His9Gln) 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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPME1 NM_016147.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0430

Genes affected

PPME1 (HGNC:30178): (protein phosphatase methylesterase 1) This gene encodes a protein phosphatase methylesterase localized to the nucleus. The encoded protein acts on the protein phosphatase-2A catalytic subunit and supports the ERK pathway through dephosphorylation of regulatory proteins. It plays a role in malignant glioma progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2012]

PPME1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14322704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPME1	NM_016147.3	c.27C>A	p.His9Gln	missense_variant	1/14	ENST00000328257.13	NP_057231.1
PPME1	NM_001271593.2	c.27C>A	p.His9Gln	missense_variant	1/14		NP_001258522.1
PPME1	XM_047427116.1	c.27C>A	p.His9Gln	missense_variant	1/12		XP_047283072.1
PPME1	XM_017017913.3	c.27C>A	p.His9Gln	missense_variant	1/10		XP_016873402.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPME1	ENST00000328257.13	c.27C>A	p.His9Gln	missense_variant	1/14	1	NM_016147.3	ENSP00000329867.8
PPME1	ENST00000398427.6	c.27C>A	p.His9Gln	missense_variant	1/14	1		ENSP00000381461.4
PPME1	ENST00000542710.3	n.182C>A		non_coding_transcript_exon_variant	1/4	3
PPME1	ENST00000544401.2	n.106C>A		non_coding_transcript_exon_variant	1/5	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.27C>A (p.H9Q) alteration is located in exon 1 (coding exon 1) of the PPME1 gene. This alteration results from a C to A substitution at nucleotide position 27, causing the histidine (H) at amino acid position 9 to be replaced by a glutamine (Q). 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	Benign	0.17
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.79	N;N
REVEL	Benign	0.17
Sift	Benign	0.11	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.0	B;.
Vest4		0.31
MutPred		0.18		Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);
MVP		0.33
MPC		0.44
ClinPred		0.34	T
GERP RS		3.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.45

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: chr11-73882493;