Variant 22-43498317-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001044370.2(MPPED1):c.715G>A(p.Val239Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,535,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00020 ( 0 hom. )

Consequence

MPPED1
NM_001044370.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

Variant links:

Genes affected

MPPED1 (HGNC:1306): (metallophosphoesterase domain containing 1) Predicted to enable hydrolase activity. [provided by Alliance of Genome Resources, Apr 2022]

MPPED1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.026643068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPPED1	NM_001044370.2 linkuse as main transcript	c.715G>A	p.Val239Ile	missense_variant	5/7	ENST00000443721.2
MPPED1	NM_001362786.2 linkuse as main transcript	c.715G>A	p.Val239Ile	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPPED1	ENST00000443721.2 linkuse as main transcript	c.715G>A	p.Val239Ile	missense_variant	5/7	2	NM_001044370.2	P1	O15442-1
MPPED1	ENST00000417669.6 linkuse as main transcript	c.715G>A	p.Val239Ile	missense_variant	5/7	5		P1	O15442-1

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000221

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000163

AC:

AN:

140724

Hom.:

AF XY:

0.000159

AC XY:

AN XY:

75426

show subpopulations

Gnomad AFR exome

AF:

0.000661

Gnomad AMR exome

AF:

0.0000409

Gnomad ASJ exome

AF:

0.000119

Gnomad EAS exome

AF:

0.0000942

Gnomad SAS exome

AF:

0.0000441

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000244

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000197

AC:

273

AN:

1383050

Hom.:

Cov.:

AF XY:

0.000182

AC XY:

124

AN XY:

682454

show subpopulations

Gnomad4 AFR exome

AF:

0.000728

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000112

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000211

Gnomad4 OTH exome

AF:

0.000259

GnomAD4 genome

AF:

0.000282

AC:

AN:

152282

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000650

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000221

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000217

Hom.:

Bravo

AF:

0.000276

ExAC

AF:

0.000229

AC:

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

May 30, 2023

The c.715G>A (p.V239I) alteration is located in exon (coding exon ) of the MPPED1 gene. This alteration results from a G to A substitution at nucleotide position 715, causing the valine (V) at amino acid position 239 to be replaced by an isoleucine (I). 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

0.074

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Benign

0.90

DEOGEN2

Benign

0.30

T;T

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.63

M_CAP

Benign

0.0047

MetaRNN

Benign

0.027

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.76

N;N

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.44

N;N

REVEL

Benign

0.13

Sift

Benign

0.71

T;T

Sift4G

Benign

0.55

T;T

Polyphen

0.011

B;B

Vest4

0.11

MVP

0.23

MPC

0.62

ClinPred

0.020

GERP RS

2.6

Varity_R

0.036

gMVP

0.66

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

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