Variant 4-87844990-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020203.6(MEPE):c.122A>T(p.Asn41Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000443 in 1,544,798 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00039 ( 6 hom. )

Consequence

MEPE
NM_020203.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.564

Variant links:

Genes affected

MEPE (HGNC:13361): (matrix extracellular phosphoglycoprotein) This gene encodes a secreted calcium-binding phosphoprotein that belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family of proteins. Members of this family are components of the extracellular matrix of bone and dentin and regulate bone mineralization. Deficiency of a similar protein in mouse results in increased bone mass. Mice lacking this gene are resistant to aging-related trabecular bone loss. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

MEPE links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0057021677).

BP6

Variant 4-87844990-A-T is Benign according to our data. Variant chr4-87844990-A-T is described in ClinVar as [Benign]. Clinvar id is 3042443.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEPE	NM_020203.6 linkuse as main transcript	c.122A>T	p.Asn41Ile	missense_variant	4/4	ENST00000361056.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEPE	ENST00000361056.4 linkuse as main transcript	c.122A>T	p.Asn41Ile	missense_variant	4/4	1	NM_020203.6	P2	Q9NQ76-1

Frequencies

GnomAD3 genomes

AF:

0.000893

AC:

136

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00236

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00684

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00100

AC:

206

AN:

205346

Hom.:

AF XY:

0.00116

AC XY:

130

AN XY:

112448

show subpopulations

Gnomad AFR exome

AF:

0.00231

Gnomad AMR exome

AF:

0.000287

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000649

Gnomad SAS exome

AF:

0.00709

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000998

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000392

AC:

546

AN:

1392468

Hom.:

Cov.:

AF XY:

0.000476

AC XY:

328

AN XY:

688868

show subpopulations

Gnomad4 AFR exome

AF:

0.00299

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00517

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000231

Gnomad4 OTH exome

AF:

0.000752

GnomAD4 genome

AF:

0.000912

AC:

139

AN:

152330

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00243

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00684

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000137

Hom.:

Bravo

AF:

0.000824

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00122

AC:

148

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MEPE-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 07, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Uncertain

0.43

T;.;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.78

T;T;T;.

MetaRNN

Benign

0.0057

T;T;T;T

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.0

M;.;.;M

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.37

PROVEAN

Pathogenic

-6.7

D;D;D;D

REVEL

Benign

0.064

Sift

Benign

0.038

D;D;D;D

Sift4G

Pathogenic

0.0010

D;D;D;D

Polyphen

0.86

P;.;.;P

Vest4

0.17

MVP

0.67

MPC

0.052

ClinPred

0.035

GERP RS

1.3

Varity_R

0.28

gMVP

0.14

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