Variant 6-46793679-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_005588.3(MEP1A):c.108T>A(p.Asp36Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,457,976 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MEP1A
NM_005588.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.14

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07871038).

BP6

Variant 6-46793679-T-A is Benign according to our data. Variant chr6-46793679-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3294246.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEP1A	NM_005588.3 link	c.108T>A	p.Asp36Glu	missense_variant	3/14	ENST00000230588.9	NP_005579.2	Q16819
MEP1A	XM_011514628.2 link	c.192T>A	p.Asp64Glu	missense_variant	2/13		XP_011512930.1	B7ZL91
MEP1A	XM_011514629.3 link	c.108T>A	p.Asp36Glu	missense_variant	3/14		XP_011512931.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MEP1A	ENST00000230588.9 link	c.108T>A	p.Asp36Glu	missense_variant	3/14	1	NM_005588.3	ENSP00000230588.4	Q16819
MEP1A	ENST00000611727.2 link	c.192T>A	p.Asp64Glu	missense_variant	2/13	1		ENSP00000480465.1	B7ZL91
MEP1A	ENST00000680229.1 link	n.108T>A		non_coding_transcript_exon_variant	3/14			ENSP00000505289.1	A0A7P0Z478
MEP1A	ENST00000680769.1 link	n.289T>A		non_coding_transcript_exon_variant	1/12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

249858

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135168

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000582

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1457976

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 02, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.042

DANN

Benign

0.60

DEOGEN2

Benign

0.19

T;.

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.46

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.079

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.2

N;.

REVEL

Benign

0.022

Sift

Benign

0.041

D;.

Sift4G

Benign

0.17

T;T

Polyphen

0.018

B;B

Vest4

0.11

MutPred

0.38

Gain of disorder (P = 0.1148);.;

MVP

0.17

MPC

0.099

ClinPred

0.091

GERP RS

-11

Varity_R

0.080

gMVP

0.38

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over