rs3812052

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000503335.7(MEGF10):c.3387T>A(p.Gly1129=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,440 control chromosomes in the GnomAD database, including 275,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 20146 hom., cov: 32)

Exomes 𝑓: 0.58 ( 255403 hom. )

Consequence

MEGF10
ENST00000503335.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.65

Variant links:

Genes affected

MEGF10 (HGNC:29634): (multiple EGF like domains 10) This gene encodes a member of the multiple epidermal growth factor-like domains protein family. The encoded protein plays a role in cell adhesion, motility and proliferation, and is a critical mediator of apoptotic cell phagocytosis as well as amyloid-beta peptide uptake in the brain. Expression of this gene may be associated with schizophrenia, and mutations in this gene are a cause of early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD) as well as congenital myopathy with minicores. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Apr 2012]

MEGF10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 5-127457282-T-A is Benign according to our data. Variant chr5-127457282-T-A is described in ClinVar as [Benign]. Clinvar id is 262076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-127457282-T-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF10	NM_001256545.2 linkuse as main transcript	c.3387T>A	p.Gly1129=	synonymous_variant	25/25	ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7 linkuse as main transcript	c.3387T>A	p.Gly1129=	synonymous_variant	25/25	1	NM_001256545.2	ENSP00000423354	P1	Q96KG7-1
MEGF10	ENST00000274473.6 linkuse as main transcript	c.3387T>A	p.Gly1129=	synonymous_variant	26/26	1		ENSP00000274473	P1	Q96KG7-1
MEGF10	ENST00000515622.1 linkuse as main transcript	n.433+1675T>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.484

AC:

73459

AN:

151854

Hom.:

20144

Cov.:

show subpopulations

Gnomad AFR

AF:

0.226

Gnomad AMI

AF:

0.754

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.597

Gnomad EAS

AF:

0.299

Gnomad SAS

AF:

0.445

Gnomad FIN

AF:

0.602

Gnomad MID

AF:

0.671

Gnomad NFE

AF:

0.622

Gnomad OTH

AF:

0.523

GnomAD3 exomes

AF:

0.528

AC:

132339

AN:

250420

Hom.:

37206

AF XY:

0.538

AC XY:

72844

AN XY:

135276

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.461

Gnomad ASJ exome

AF:

0.601

Gnomad EAS exome

AF:

0.294

Gnomad SAS exome

AF:

0.471

Gnomad FIN exome

AF:

0.601

Gnomad NFE exome

AF:

0.624

Gnomad OTH exome

AF:

0.574

GnomAD4 exome

AF:

0.584

AC:

853559

AN:

1461468

Hom.:

255403

Cov.:

AF XY:

0.584

AC XY:

424335

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.214

Gnomad4 AMR exome

AF:

0.467

Gnomad4 ASJ exome

AF:

0.608

Gnomad4 EAS exome

AF:

0.292

Gnomad4 SAS exome

AF:

0.478

Gnomad4 FIN exome

AF:

0.602

Gnomad4 NFE exome

AF:

0.618

Gnomad4 OTH exome

AF:

0.562

GnomAD4 genome

AF:

0.483

AC:

73466

AN:

151972

Hom.:

20146

Cov.:

AF XY:

0.483

AC XY:

35869

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.226

Gnomad4 AMR

AF:

0.505

Gnomad4 ASJ

AF:

0.597

Gnomad4 EAS

AF:

0.299

Gnomad4 SAS

AF:

0.446

Gnomad4 FIN

AF:

0.602

Gnomad4 NFE

AF:

0.622

Gnomad4 OTH

AF:

0.527

Alfa

AF:

0.585

Hom.:

8609

Bravo

AF:

0.466

Asia WGS

AF:

0.398

AC:

1383

AN:

3478

EpiCase

AF:

0.633

EpiControl

AF:

0.641

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 53% of total chromosomes in ExAC -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2016	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

MEGF10-related myopathy

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.12

DANN

Benign

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