Variant 18-11888709-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_023075.6(MPPE1):c.529G>C(p.Val177Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,448,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

MPPE1
NM_023075.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.32

Variant links:

Genes affected

MPPE1 (HGNC:15988): (metallophosphoesterase 1) Predicted to enable GPI anchor binding activity; GPI-mannose ethanolamine phosphate phosphodiesterase activity; and manganese ion binding activity. Involved in GPI anchor biosynthetic process. Located in Golgi apparatus and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MPPE1 links:

MPPE1 (HGNC:):

MPPE1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.18880937).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPPE1	NM_023075.6 linkuse as main transcript	c.529G>C	p.Val177Leu	missense_variant	6/11	ENST00000588072.6	NP_075563.3	Q53F39-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPPE1	ENST00000588072.6 linkuse as main transcript	c.529G>C	p.Val177Leu	missense_variant	6/11	1	NM_023075.6	ENSP00000465894.1		Q53F39-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1448008

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

720590

show subpopulations

Gnomad4 AFR exome

AF:

0.0000307

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:

0.00000271

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 07, 2022

The c.529G>C (p.V177L) alteration is located in exon 6 (coding exon 4) of the MPPE1 gene. This alteration results from a G to C substitution at nucleotide position 529, causing the valine (V) at amino acid position 177 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

Benign

0.25

BayesDel_addAF

Benign

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.26

T;.;.;T;.;T;.

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.20

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;.;T;T;T;T;T

M_CAP

Benign

0.020

MetaRNN

Benign

0.19

T;T;T;T;T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.3

M;M;M;.;.;.;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.6

.;N;N;N;.;.;.

REVEL

Benign

0.076

Sift

Benign

0.35

.;T;T;T;.;.;.

Sift4G

Benign

0.38

T;T;T;T;T;.;T

Polyphen

0.022

B;P;P;.;.;.;.

Vest4

0.41

MutPred

0.47

Loss of methylation at K176 (P = 0.0887);Loss of methylation at K176 (P = 0.0887);Loss of methylation at K176 (P = 0.0887);Loss of methylation at K176 (P = 0.0887);Loss of methylation at K176 (P = 0.0887);.;Loss of methylation at K176 (P = 0.0887);

MVP

0.63

MPC

0.16

ClinPred

0.60

GERP RS

4.8

Varity_R

0.21

gMVP

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over