11-74225230-A-T

Position:

• chr11-74225230-A-T

Variant summary

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

The NM_016147.3(PPME1):​c.372A>T​(p.Glu124Asp) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPME1 NM_016147.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07

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]

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=0.07373911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPME1	NM_016147.3	c.372A>T	p.Glu124Asp	missense_variant	5/14	ENST00000328257.13
PPME1	NM_001271593.2	c.372A>T	p.Glu124Asp	missense_variant	5/14
PPME1	XM_047427116.1	c.372A>T	p.Glu124Asp	missense_variant	5/12
PPME1	XM_017017913.3	c.372A>T	p.Glu124Asp	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPME1	ENST00000328257.13	c.372A>T	p.Glu124Asp	missense_variant	5/14	1	NM_016147.3	P1
PPME1	ENST00000398427.6	c.372A>T	p.Glu124Asp	missense_variant	5/14	1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1418044 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 702404

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	19
DANN	Benign	0.40
DEOGEN2	Benign	0.067	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.074	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.33	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.53	N;N
REVEL	Benign	0.093
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;.
Vest4		0.17
MutPred		0.34		Gain of ubiquitination at K119 (P = 0.2251);Gain of ubiquitination at K119 (P = 0.2251);
MVP		0.18
MPC		0.40
ClinPred		0.36	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.23
gMVP		0.61

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

LitVar

Other links and lift over

dbSNP: rs1858904107; hg19: chr11-73936275;