Variant 6-46826454-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005588.3(MEP1A):c.879C>G(p.Asp293Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000688 in 1,453,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000069 ( 0 hom. )

Consequence

MEP1A
NM_005588.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.470

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0958375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEP1A	NM_005588.3 link	c.879C>G	p.Asp293Glu	missense_variant	9/14	ENST00000230588.9	NP_005579.2	Q16819
MEP1A	XM_011514628.2 link	c.963C>G	p.Asp321Glu	missense_variant	8/13		XP_011512930.1	B7ZL91
MEP1A	XM_011514629.3 link	c.879C>G	p.Asp293Glu	missense_variant	9/14		XP_011512931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEP1A	ENST00000230588.9 link	c.879C>G	p.Asp293Glu	missense_variant	9/14	1	NM_005588.3	ENSP00000230588.4		Q16819

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000162

AC:

AN:

246682

Hom.:

AF XY:

0.0000225

AC XY:

AN XY:

133232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000688

AC:

AN:

1453706

Hom.:

Cov.:

AF XY:

0.00000553

AC XY:

AN XY:

722678

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000902

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2023

The c.879C>G (p.D293E) alteration is located in exon 9 (coding exon 9) of the MEP1A gene. This alteration results from a C to G substitution at nucleotide position 879, causing the aspartic acid (D) at amino acid position 293 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.9

DANN

Benign

0.95

DEOGEN2

Benign

0.041

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.082

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

L;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.44

N;.

REVEL

Benign

0.13

Sift

Benign

0.62

T;.

Sift4G

Benign

0.85

T;T

Polyphen

0.24

B;B

Vest4

0.076

MutPred

0.37

Gain of sheet (P = 0.1945);.;

MVP

0.32

MPC

0.097

ClinPred

0.097

GERP RS

4.8

Varity_R

0.13

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over