Variant 4-87845484-A-G 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.616A>G(p.Ser206Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00336 in 1,613,824 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S206I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0035 ( 20 hom. )

Consequence

MEPE
NM_020203.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.337

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=0.0065416694).

BP6

Variant 4-87845484-A-G is Benign according to our data. Variant chr4-87845484-A-G is described in ClinVar as [Benign]. Clinvar id is 3038619.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEPE	NM_020203.6 linkuse as main transcript	c.616A>G	p.Ser206Gly	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.616A>G	p.Ser206Gly	missense_variant	4/4	1	NM_020203.6	P2	Q9NQ76-1

Frequencies

GnomAD3 genomes

AF:

0.00219

AC:

333

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00268

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00290

AC:

725

AN:

249652

Hom.:

AF XY:

0.00286

AC XY:

387

AN XY:

135112

show subpopulations

Gnomad AFR exome

AF:

0.000311

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.000698

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0135

Gnomad NFE exome

AF:

0.00363

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00348

AC:

5086

AN:

1461516

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

2424

AN XY:

727092

show subpopulations

Gnomad4 AFR exome

AF:

0.000359

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0117

Gnomad4 NFE exome

AF:

0.00382

Gnomad4 OTH exome

AF:

0.00295

GnomAD4 genome

AF:

0.00219

AC:

333

AN:

152308

Hom.:

Cov.:

AF XY:

0.00259

AC XY:

193

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0124

Gnomad4 NFE

AF:

0.00268

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00262

Hom.:

Bravo

AF:

0.00155

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00269

AC:

327

EpiCase

AF:

0.00251

EpiControl

AF:

0.00202

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

May 23, 2019

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

0.073

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

Cadd

Benign

0.45

Dann

Benign

0.44

DEOGEN2

Benign

0.18

T;.;.;.;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.49

T;T;T;.;T;.

MetaRNN

Benign

0.0065

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.83

L;.;.;.;.;L

MutationTaster

Benign

1.0

N;N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.4

N;N;N;N;N;N

REVEL

Benign

0.016

Sift

Benign

0.35

T;T;T;T;T;T

Sift4G

Benign

0.43

T;T;T;T;T;T

Polyphen

0.0020

B;.;.;.;.;B

Vest4

0.052

MVP

0.30

MPC

0.032

ClinPred

0.019

GERP RS

-2.1

Varity_R

0.066

gMVP

0.031

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