Variant rs2297019 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005588.3(MEP1A):c.1900A>G(p.Met634Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 1,610,370 control chromosomes in the GnomAD database, including 56,640 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.31 ( 8060 hom., cov: 32)

Exomes 𝑓: 0.25 ( 48580 hom. )

Consequence

MEP1A
NM_005588.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.85

Variant links:

Genes affected

MEP1A (HGNC:7015): (meprin A subunit alpha) Predicted to enable metalloendopeptidase activity. Predicted to be involved in proteolysis. Located in extracellular exosome. Part of meprin A complex. [provided by Alliance of Genome Resources, Apr 2022]

MEP1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2250414E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MEP1A	NM_005588.3 linkuse as main transcript	c.1900A>G	p.Met634Val	missense_variant	13/14	ENST00000230588.9
MEP1A	XM_011514628.2 linkuse as main transcript	c.1984A>G	p.Met662Val	missense_variant	12/13
MEP1A	XM_011514629.3 linkuse as main transcript	c.1900A>G	p.Met634Val	missense_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MEP1A	ENST00000230588.9 linkuse as main transcript	c.1900A>G	p.Met634Val	missense_variant	13/14	1	NM_005588.3	P1
MEP1A	ENST00000611727.2 linkuse as main transcript	c.1984A>G	p.Met662Val	missense_variant	12/13	1
MEP1A	ENST00000680769.1 linkuse as main transcript	n.2081A>G		non_coding_transcript_exon_variant	11/12
MEP1A	ENST00000680229.1 linkuse as main transcript	c.*1085A>G		3_prime_UTR_variant, NMD_transcript_variant	13/14

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46818

AN:

152018

Hom.:

8041

Cov.:

show subpopulations

Gnomad AFR

AF:

0.460

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.302

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.317

Gnomad FIN

AF:

0.195

Gnomad MID

AF:

0.236

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.291

GnomAD3 exomes

AF:

0.277

AC:

67879

AN:

244688

Hom.:

9773

AF XY:

0.272

AC XY:

35984

AN XY:

132266

show subpopulations

Gnomad AFR exome

AF:

0.461

Gnomad AMR exome

AF:

0.321

Gnomad ASJ exome

AF:

0.301

Gnomad EAS exome

AF:

0.289

Gnomad SAS exome

AF:

0.308

Gnomad FIN exome

AF:

0.198

Gnomad NFE exome

AF:

0.242

Gnomad OTH exome

AF:

0.250

GnomAD4 exome

AF:

0.254

AC:

370044

AN:

1458234

Hom.:

48580

Cov.:

AF XY:

0.254

AC XY:

184100

AN XY:

725060

show subpopulations

Gnomad4 AFR exome

AF:

0.464

Gnomad4 AMR exome

AF:

0.319

Gnomad4 ASJ exome

AF:

0.297

Gnomad4 EAS exome

AF:

0.293

Gnomad4 SAS exome

AF:

0.307

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.265

GnomAD4 genome

AF:

0.308

AC:

46893

AN:

152136

Hom.:

8060

Cov.:

AF XY:

0.305

AC XY:

22691

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.460

Gnomad4 AMR

AF:

0.313

Gnomad4 ASJ

AF:

0.302

Gnomad4 EAS

AF:

0.281

Gnomad4 SAS

AF:

0.317

Gnomad4 FIN

AF:

0.195

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.290

Alfa

AF:

0.251

Hom.:

2596

Bravo

AF:

0.321

TwinsUK

AF:

0.248

AC:

921

ALSPAC

AF:

0.240

AC:

924

ESP6500AA

AF:

0.441

AC:

1942

ESP6500EA

AF:

0.250

AC:

2152

ExAC

AF:

0.279

AC:

33896

Asia WGS

AF:

0.292

AC:

1015

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.86

Cadd

Benign

0.0020

Dann

Benign

0.34

DEOGEN2

Benign

0.053

T;.

Eigen

Benign

-1.9

Eigen_PC

Benign

-2.0

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.21

T;T

MetaRNN

Benign

0.00022

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

0.18

N;.

REVEL

Benign

0.027

Sift

Benign

1.0

T;.

Sift4G

Benign

0.75

T;T

Polyphen

0.0

B;B

Vest4

0.052

MPC

0.10

ClinPred

0.00070

GERP RS

-6.7

Varity_R

0.022

gMVP

0.29

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over