Variant rs2297020 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.1816A>T(p.Thr606Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,600,788 control chromosomes in the GnomAD database, including 54,302 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 0.29 ( 7051 hom., cov: 32)

Exomes 𝑓: 0.25 ( 47251 hom. )

Consequence

MEP1A
NM_005588.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.784

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=4.5639277E-4).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MEP1A	NM_005588.3 linkuse as main transcript	c.1816A>T	p.Thr606Ser	missense_variant	13/14	ENST00000230588.9
MEP1A	XM_011514628.2 linkuse as main transcript	c.1900A>T	p.Thr634Ser	missense_variant	12/13
MEP1A	XM_011514629.3 linkuse as main transcript	c.1816A>T	p.Thr606Ser	missense_variant	13/14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MEP1A	ENST00000230588.9 linkuse as main transcript	c.1816A>T	p.Thr606Ser	missense_variant	13/14	1	NM_005588.3	P1
MEP1A	ENST00000611727.2 linkuse as main transcript	c.1900A>T	p.Thr634Ser	missense_variant	12/13	1
MEP1A	ENST00000680769.1 linkuse as main transcript	n.1997A>T		non_coding_transcript_exon_variant	11/12
MEP1A	ENST00000680229.1 linkuse as main transcript	c.*1001A>T		3_prime_UTR_variant, NMD_transcript_variant	13/14

Frequencies

GnomAD3 genomes

AF:

0.293

AC:

44468

AN:

151900

Hom.:

7037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.158

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.321

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.278

GnomAD3 exomes

AF:

0.272

AC:

62670

AN:

230770

Hom.:

8724

AF XY:

0.268

AC XY:

33323

AN XY:

124404

show subpopulations

Gnomad AFR exome

AF:

0.403

Gnomad AMR exome

AF:

0.316

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.289

Gnomad SAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.196

Gnomad NFE exome

AF:

0.240

Gnomad OTH exome

AF:

0.245

GnomAD4 exome

AF:

0.252

AC:

365050

AN:

1448770

Hom.:

47251

Cov.:

AF XY:

0.252

AC XY:

181568

AN XY:

719504

show subpopulations

Gnomad4 AFR exome

AF:

0.409

Gnomad4 AMR exome

AF:

0.313

Gnomad4 ASJ exome

AF:

0.297

Gnomad4 EAS exome

AF:

0.294

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.262

GnomAD4 genome

AF:

0.293

AC:

44530

AN:

152018

Hom.:

7051

Cov.:

AF XY:

0.290

AC XY:

21583

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.307

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.283

Gnomad4 SAS

AF:

0.321

Gnomad4 FIN

AF:

0.194

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.255

Hom.:

1703

Bravo

AF:

0.303

TwinsUK

AF:

0.248

AC:

921

ALSPAC

AF:

0.240

AC:

924

ESP6500AA

AF:

0.392

AC:

1728

ESP6500EA

AF:

0.247

AC:

2119

ExAC

AF:

0.265

AC:

32099

Asia WGS

AF:

0.293

AC:

1017

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.74

DANN

Benign

0.71

DEOGEN2

Benign

0.085

T;.

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.00046

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

N;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.0

N;.

REVEL

Benign

0.063

Sift

Benign

0.097

T;.

Sift4G

Benign

0.086

T;T

Polyphen

0.025

B;B

Vest4

0.14

MutPred

0.064

Loss of glycosylation at T606 (P = 0.0421);.;

MPC

0.098

ClinPred

0.019

GERP RS

-10

Varity_R

0.047

gMVP

0.19

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