Variant 4-87845116-G-A 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_020203.6(MEPE):c.248G>A(p.Ser83Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,461,476 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 0.000034 ( 0 hom. )

Consequence

MEPE
NM_020203.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0620

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:

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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=0.15493968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEPE	NM_020203.6 linkuse as main transcript	c.248G>A	p.Ser83Asn	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.248G>A	p.Ser83Asn	missense_variant	4/4	1	NM_020203.6	P2	Q9NQ76-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249982

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000884

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461476

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

727026

show subpopulations

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:

0.0000423

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000312

Hom.:

Bravo

AF:

0.00000756

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 09, 2022

The c.248G>A (p.S83N) alteration is located in exon 4 (coding exon 3) of the MEPE gene. This alteration results from a G to A substitution at nucleotide position 248, causing the serine (S) at amino acid position 83 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.24

T;.;.;T

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.53

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.56

T;T;T;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.15

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.2

M;.;.;M

MutationTaster

Benign

1.0

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

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.1

N;N;N;N

REVEL

Benign

0.075

Sift

Benign

0.038

D;D;D;D

Sift4G

Uncertain

0.044

D;T;D;D

Polyphen

0.80

P;.;.;P

Vest4

0.056

MutPred

0.51

Gain of relative solvent accessibility (P = 0.0166);.;.;Gain of relative solvent accessibility (P = 0.0166);

MVP

0.64

MPC

0.11

ClinPred

0.54

GERP RS

2.0

Varity_R

0.076

gMVP

0.094

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