Genetic Variant MEPE:p.Pro58Arg (chr4-87839749-C-G) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001291183.2(MEPE):c.173C>G(p.Pro58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000231 in 1,550,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

MEPE
NM_001291183.2 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.732

Publications

1 publications found

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:

ENSG00000307815 (HGNC:58843):

ENSG00000307815 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0055841804).

BP6

Variant 4-87839749-C-G is Benign according to our data. Variant chr4-87839749-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3352748.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291183.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEPE	NM_020203.6	MANE Select	c.108+1064C>G		intron	N/A	NP_064588.1	Q9NQ76-1
MEPE	NM_001291183.2		c.173C>G	p.Pro58Arg	missense	Exon 4 of 5	NP_001278112.1	Q9NQ76-2
MEPE	NM_001184697.2		c.-366C>G		5_prime_UTR	Exon 4 of 6	NP_001171626.1	Q9NQ76-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEPE	ENST00000560249.6	TSL:1	c.173C>G	p.Pro58Arg	missense	Exon 4 of 6	ENSP00000453994.2	A0A8J9B5S1
MEPE	ENST00000361056.4	TSL:1 MANE Select	c.108+1064C>G		intron	N/A	ENSP00000354341.3	Q9NQ76-1
MEPE	ENST00000395102.8	TSL:5	c.173C>G	p.Pro58Arg	missense	Exon 4 of 5	ENSP00000378534.4	Q9NQ76-2

Frequencies

GnomAD3 genomes

AF:

0.00103

AC:

157

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00343

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000369

AC:

AN:

148894

AF XY:

0.000312

show subpopulations

Gnomad AFR exome

AF:

0.00563

Gnomad AMR exome

AF:

0.000652

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000144

AC:

201

AN:

1397864

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

689476

show subpopulations

African (AFR)

AF:

0.00405

AC:

128

AN:

31578

American (AMR)

AF:

0.000448

AC:

AN:

35692

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48164

Middle Eastern (MID)

AF:

0.000702

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1078626

Other (OTH)

AF:

0.000345

AC:

AN:

57984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00103

AC:

157

AN:

152214

Hom.:

Cov.:

AF XY:

0.000995

AC XY:

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00342

AC:

142

AN:

41548

American (AMR)

AF:

0.000327

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000208

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68004

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000313

Hom.:

Bravo

AF:

0.00114

ExAC

AF:

0.000151

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

MEPE-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.70

M_CAP

Benign

0.0024

MetaRNN

Benign

0.0056

MetaSVM

Benign

-0.99

PhyloP100

0.73

PROVEAN

Uncertain

-3.2

REVEL

Benign

0.018

Sift

Uncertain

0.0060

Sift4G

Benign

0.076

Vest4

0.22

MVP

0.38

ClinPred

0.032

GERP RS

2.6

gMVP

0.083

Mutation Taster

=294/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over