Variant rs2274658 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.1405G>T(p.Val469Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 1,613,798 control chromosomes in the GnomAD database, including 128,185 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 0.42 ( 13963 hom., cov: 32)

Exomes 𝑓: 0.39 ( 114222 hom. )

Consequence

MEP1A
NM_005588.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.614

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:

MEP1A (HGNC:):

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=3.346789E-5).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEP1A	NM_005588.3 linkuse as main transcript	c.1405G>T	p.Val469Leu	missense_variant	11/14	ENST00000230588.9	NP_005579.2	Q16819
MEP1A	XM_011514628.2 linkuse as main transcript	c.1489G>T	p.Val497Leu	missense_variant	10/13		XP_011512930.1	B7ZL91
MEP1A	XM_011514629.3 linkuse as main transcript	c.1405G>T	p.Val469Leu	missense_variant	11/14		XP_011512931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEP1A	ENST00000230588.9 linkuse as main transcript	c.1405G>T	p.Val469Leu	missense_variant	11/14	1	NM_005588.3	ENSP00000230588.4		Q16819

Frequencies

GnomAD3 genomes

AF:

0.423

AC:

64242

AN:

151924

Hom.:

13946

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.521

Gnomad AMR

AF:

0.435

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.382

Gnomad MID

AF:

0.487

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.415

GnomAD3 exomes

AF:

0.395

AC:

99288

AN:

251458

Hom.:

20444

AF XY:

0.392

AC XY:

53327

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.452

Gnomad ASJ exome

AF:

0.408

Gnomad EAS exome

AF:

0.183

Gnomad SAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.389

Gnomad NFE exome

AF:

0.392

Gnomad OTH exome

AF:

0.415

GnomAD4 exome

AF:

0.392

AC:

572900

AN:

1461756

Hom.:

114222

Cov.:

AF XY:

0.392

AC XY:

285410

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.511

Gnomad4 AMR exome

AF:

0.453

Gnomad4 ASJ exome

AF:

0.407

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.404

Gnomad4 FIN exome

AF:

0.389

Gnomad4 NFE exome

AF:

0.391

Gnomad4 OTH exome

AF:

0.402

GnomAD4 genome

AF:

0.423

AC:

64307

AN:

152042

Hom.:

13963

Cov.:

AF XY:

0.421

AC XY:

31295

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.499

Gnomad4 AMR

AF:

0.435

Gnomad4 ASJ

AF:

0.389

Gnomad4 EAS

AF:

0.189

Gnomad4 SAS

AF:

0.407

Gnomad4 FIN

AF:

0.382

Gnomad4 NFE

AF:

0.400

Gnomad4 OTH

AF:

0.417

Alfa

AF:

0.398

Hom.:

17645

Bravo

AF:

0.431

TwinsUK

AF:

0.391

AC:

1451

ALSPAC

AF:

0.394

AC:

1519

ESP6500AA

AF:

0.505

AC:

2227

ESP6500EA

AF:

0.397

AC:

3416

ExAC

AF:

0.394

AC:

47851

Asia WGS

AF:

0.367

AC:

1278

AN:

3478

EpiCase

AF:

0.401

EpiControl

AF:

0.396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

1.5

DANN

Benign

0.66

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.48

T;T

MetaRNN

Benign

0.000033

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.59

N;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.5

N;.

REVEL

Benign

0.027

Sift

Benign

0.32

T;.

Sift4G

Benign

0.40

T;T

Polyphen

0.0040

B;B

Vest4

0.026

MutPred

0.17

Gain of disorder (P = 0.1676);.;

MPC

0.10

ClinPred

0.0021

GERP RS

1.2

Varity_R

0.064

gMVP

0.13

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