Variant rs12197930 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.1426A>G(p.Arg476Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0361 in 1,614,164 control chromosomes in the GnomAD database, including 1,300 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.045 ( 164 hom., cov: 32)

Exomes 𝑓: 0.035 ( 1136 hom. )

Consequence

MEP1A
NM_005588.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.622

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=0.0025639832).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MEP1A	NM_005588.3 linkuse as main transcript	c.1426A>G	p.Arg476Gly	missense_variant	11/14	ENST00000230588.9
MEP1A	XM_011514628.2 linkuse as main transcript	c.1510A>G	p.Arg504Gly	missense_variant	10/13
MEP1A	XM_011514629.3 linkuse as main transcript	c.1426A>G	p.Arg476Gly	missense_variant	11/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MEP1A	ENST00000230588.9 linkuse as main transcript	c.1426A>G	p.Arg476Gly	missense_variant	11/14	1	NM_005588.3	P1
MEP1A	ENST00000611727.2 linkuse as main transcript	c.1510A>G	p.Arg504Gly	missense_variant	10/13	1
MEP1A	ENST00000680769.1 linkuse as main transcript	n.1607A>G		non_coding_transcript_exon_variant	9/12
MEP1A	ENST00000680229.1 linkuse as main transcript	c.*611A>G		3_prime_UTR_variant, NMD_transcript_variant	11/14

Frequencies

GnomAD3 genomes

AF:

0.0453

AC:

6896

AN:

152224

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0712

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0387

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.0136

Gnomad SAS

AF:

0.0612

Gnomad FIN

AF:

0.0276

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0341

Gnomad OTH

AF:

0.0492

GnomAD3 exomes

AF:

0.0420

AC:

10569

AN:

251478

Hom.:

296

AF XY:

0.0426

AC XY:

5785

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0747

Gnomad AMR exome

AF:

0.0412

Gnomad ASJ exome

AF:

0.0697

Gnomad EAS exome

AF:

0.0145

Gnomad SAS exome

AF:

0.0707

Gnomad FIN exome

AF:

0.0296

Gnomad NFE exome

AF:

0.0344

Gnomad OTH exome

AF:

0.0401

GnomAD4 exome

AF:

0.0352

AC:

51456

AN:

1461822

Hom.:

1136

Cov.:

AF XY:

0.0366

AC XY:

26600

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.0698

Gnomad4 AMR exome

AF:

0.0405

Gnomad4 ASJ exome

AF:

0.0712

Gnomad4 EAS exome

AF:

0.0126

Gnomad4 SAS exome

AF:

0.0682

Gnomad4 FIN exome

AF:

0.0291

Gnomad4 NFE exome

AF:

0.0311

Gnomad4 OTH exome

AF:

0.0403

GnomAD4 genome

AF:

0.0452

AC:

6891

AN:

152342

Hom.:

164

Cov.:

AF XY:

0.0440

AC XY:

3279

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0710

Gnomad4 AMR

AF:

0.0385

Gnomad4 ASJ

AF:

0.0599

Gnomad4 EAS

AF:

0.0137

Gnomad4 SAS

AF:

0.0609

Gnomad4 FIN

AF:

0.0276

Gnomad4 NFE

AF:

0.0342

Gnomad4 OTH

AF:

0.0482

Alfa

AF:

0.0389

Hom.:

154

Bravo

AF:

0.0473

TwinsUK

AF:

0.0289

AC:

107

ALSPAC

AF:

0.0319

AC:

123

ESP6500AA

AF:

0.0744

AC:

328

ESP6500EA

AF:

0.0348

AC:

299

ExAC

AF:

0.0430

AC:

5216

Asia WGS

AF:

0.0400

AC:

142

AN:

3478

EpiCase

AF:

0.0324

EpiControl

AF:

0.0356

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.5

DANN

Benign

0.63

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.65

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.8

N;.

REVEL

Benign

0.034

Sift

Benign

0.38

T;.

Sift4G

Benign

0.42

T;T

Polyphen

0.0040

B;B

Vest4

0.26

MPC

0.14

ClinPred

0.0046

GERP RS

0.12

Varity_R

0.064

gMVP

0.25

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