rs56157640

Positions:

chr5-127455564-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The ENST00000503335.7(MEGF10):c.3189G>A(p.Glu1063=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,614,078 control chromosomes in the GnomAD database, including 602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 54 hom., cov: 32)

Exomes 𝑓: 0.022 ( 548 hom. )

Consequence

MEGF10
ENST00000503335.7 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.59

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 5-127455564-G-A is Benign according to our data. Variant chr5-127455564-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 380909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0713 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.3189G>A	p.Glu1063=	synonymous_variant	24/25	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.3189G>A	p.Glu1063=	synonymous_variant	24/25	1	NM_001256545.2	ENSP00000423354	P1	Q96KG7-1
MEGF10	ENST00000274473.6 linkuse as main transcript	c.3189G>A	p.Glu1063=	synonymous_variant	25/26	1		ENSP00000274473	P1	Q96KG7-1
MEGF10	ENST00000515622.1 linkuse as main transcript	n.390G>A		non_coding_transcript_exon_variant	4/5	2
MEGF10	ENST00000510828.5 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0187

AC:

2849

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00674

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0109

Gnomad ASJ

AF:

0.0476

Gnomad EAS

AF:

0.0500

Gnomad SAS

AF:

0.0775

Gnomad FIN

AF:

0.0313

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0174

Gnomad OTH

AF:

0.0201

GnomAD3 exomes

AF:

0.0266

AC:

6667

AN:

251088

Hom.:

155

AF XY:

0.0291

AC XY:

3956

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.00517

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0466

Gnomad EAS exome

AF:

0.0500

Gnomad SAS exome

AF:

0.0664

Gnomad FIN exome

AF:

0.0293

Gnomad NFE exome

AF:

0.0175

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0218

AC:

31891

AN:

1461824

Hom.:

548

Cov.:

AF XY:

0.0231

AC XY:

16829

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.00511

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.0454

Gnomad4 EAS exome

AF:

0.0387

Gnomad4 SAS exome

AF:

0.0661

Gnomad4 FIN exome

AF:

0.0293

Gnomad4 NFE exome

AF:

0.0176

Gnomad4 OTH exome

AF:

0.0252

GnomAD4 genome

AF:

0.0187

AC:

2846

AN:

152254

Hom.:

Cov.:

AF XY:

0.0206

AC XY:

1530

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.00672

Gnomad4 AMR

AF:

0.0108

Gnomad4 ASJ

AF:

0.0476

Gnomad4 EAS

AF:

0.0500

Gnomad4 SAS

AF:

0.0777

Gnomad4 FIN

AF:

0.0313

Gnomad4 NFE

AF:

0.0174

Gnomad4 OTH

AF:

0.0194

Alfa

AF:

0.0187

Hom.:

Bravo

AF:

0.0153

Asia WGS

AF:

0.0500

AC:

173

AN:

3478

EpiCase

AF:

0.0182

EpiControl

AF:

0.0156

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 10, 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, 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: 2.7% of total chromosomes in ExAC, 6.8% of S. Asian chromosomes -

MEGF10-related myopathy

Benign:2

Likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

5.5

DANN

Benign

0.47

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