rs11950427

Positions:

chr5-127433454-T-C

Variant summary

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

The NM_001256545.2(MEGF10):c.1785T>C(p.Pro595Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,613,632 control chromosomes in the GnomAD database, including 21,474 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3219 hom., cov: 33)

Exomes 𝑓: 0.15 ( 18255 hom. )

Consequence

MEGF10
NM_001256545.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -3.29

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-127433454-T-C is Benign according to our data. Variant chr5-127433454-T-C is described in ClinVar as [Benign]. Clinvar id is 262065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 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.1785T>C	p.Pro595Pro	synonymous_variant	14/25	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.1785T>C	p.Pro595Pro	synonymous_variant	14/25	1	NM_001256545.2	ENSP00000423354.2	Q96KG7-1
MEGF10	ENST00000274473.6 linkuse as main transcript	c.1785T>C	p.Pro595Pro	synonymous_variant	15/26	1		ENSP00000274473.6	Q96KG7-1
MEGF10	ENST00000506709.1 linkuse as main transcript	n.82-1233T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29225

AN:

152046

Hom.:

3213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.139

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.155

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.187

Gnomad MID

AF:

0.142

Gnomad NFE

AF:

0.153

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.155

AC:

38860

AN:

250858

Hom.:

3409

AF XY:

0.155

AC XY:

21053

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.303

Gnomad AMR exome

AF:

0.0824

Gnomad ASJ exome

AF:

0.147

Gnomad EAS exome

AF:

0.101

Gnomad SAS exome

AF:

0.175

Gnomad FIN exome

AF:

0.189

Gnomad NFE exome

AF:

0.154

Gnomad OTH exome

AF:

0.149

GnomAD4 exome

AF:

0.154

AC:

225620

AN:

1461468

Hom.:

18255

Cov.:

AF XY:

0.154

AC XY:

112188

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.302

Gnomad4 AMR exome

AF:

0.0841

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.111

Gnomad4 SAS exome

AF:

0.174

Gnomad4 FIN exome

AF:

0.190

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.152

GnomAD4 genome

AF:

0.192

AC:

29260

AN:

152164

Hom.:

3219

Cov.:

AF XY:

0.191

AC XY:

14208

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.117

Gnomad4 ASJ

AF:

0.155

Gnomad4 EAS

AF:

0.108

Gnomad4 SAS

AF:

0.200

Gnomad4 FIN

AF:

0.187

Gnomad4 NFE

AF:

0.153

Gnomad4 OTH

AF:

0.166

Alfa

AF:

0.170

Hom.:

1343

Bravo

AF:

0.189

Asia WGS

AF:

0.143

AC:

501

AN:

3478

EpiCase

AF:

0.140

EpiControl

AF:

0.137

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 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: 16% of total chromosomes in ExAC -
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 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0050

DANN

Benign

0.42

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