rs17164935

Positions:

chr5-127455590-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256545.2(MEGF10):c.3215G>A(p.Arg1072Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 1,613,490 control chromosomes in the GnomAD database, including 20,250 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1560 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18690 hom. )

Consequence

MEGF10
NM_001256545.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.40

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:

MEGF10 (HGNC:):

MEGF10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012667179).

BP6

Variant 5-127455590-G-A is Benign according to our data. Variant chr5-127455590-G-A is described in ClinVar as [Benign]. Clinvar id is 262075.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 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.3215G>A	p.Arg1072Lys	missense_variant	24/25	ENST00000503335.7	NP_001243474.1	Q96KG7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MEGF10	ENST00000503335.7 linkuse as main transcript	c.3215G>A	p.Arg1072Lys	missense_variant	24/25	1	NM_001256545.2	ENSP00000423354.2	Q96KG7-1
MEGF10	ENST00000274473.6 linkuse as main transcript	c.3215G>A	p.Arg1072Lys	missense_variant	25/26	1		ENSP00000274473.6	Q96KG7-1
MEGF10	ENST00000515622.1 linkuse as main transcript	n.416G>A		non_coding_transcript_exon_variant	4/5	2
MEGF10	ENST00000510828.5 linkuse as main transcript	n.*28G>A		downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.141

AC:

21417

AN:

152038

Hom.:

1556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.124

Gnomad AMR

AF:

0.107

Gnomad ASJ

AF:

0.128

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.134

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.135

GnomAD3 exomes

AF:

0.138

AC:

34687

AN:

250580

Hom.:

2659

AF XY:

0.140

AC XY:

18988

AN XY:

135482

show subpopulations

Gnomad AFR exome

AF:

0.105

Gnomad AMR exome

AF:

0.0776

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.0957

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.180

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.143

GnomAD4 exome

AF:

0.158

AC:

230230

AN:

1461334

Hom.:

18690

Cov.:

AF XY:

0.157

AC XY:

113846

AN XY:

726972

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.0801

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.109

Gnomad4 SAS exome

AF:

0.121

Gnomad4 FIN exome

AF:

0.183

Gnomad4 NFE exome

AF:

0.167

Gnomad4 OTH exome

AF:

0.147

GnomAD4 genome

AF:

0.141

AC:

21448

AN:

152156

Hom.:

1560

Cov.:

AF XY:

0.138

AC XY:

10282

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.111

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.128

Gnomad4 EAS

AF:

0.103

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.153

Hom.:

4085

Bravo

AF:

0.132

TwinsUK

AF:

0.171

AC:

633

ALSPAC

AF:

0.166

AC:

641

ESP6500AA

AF:

0.106

AC:

465

ESP6500EA

AF:

0.163

AC:

1404

ExAC

AF:

0.141

AC:

17180

Asia WGS

AF:

0.111

AC:

388

AN:

3478

EpiCase

AF:

0.152

EpiControl

AF:

0.149

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 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	PreventionGenetics, part of Exact Sciences	-	- -

MEGF10-related myopathy

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.011

T;T

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.32

.;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.2

N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

0.25

N;N

REVEL

Benign

0.20

Sift

Benign

1.0

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.022

MPC

0.22

ClinPred

0.0026

GERP RS

3.0

Varity_R

0.034

gMVP

0.18

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