5-127410585-C-T

Variant summary

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

The NM_001256545.2(MEGF10):​c.1114C>T​(p.Leu372Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,606,830 control chromosomes in the GnomAD database, including 691,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68318 hom., cov: 34)
Exomes 𝑓: 0.93 ( 622695 hom. )

Consequence

MEGF10
NM_001256545.2 synonymous

Scores

2

Clinical Significance

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

Conservation

PhyloP100: -0.168
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]

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=-0.64).
BP6
Variant 5-127410585-C-T is Benign according to our data. Variant chr5-127410585-C-T is described in ClinVar as [Benign]. Clinvar id is 262060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-127410585-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.168 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MEGF10NM_001256545.2 linkuse as main transcriptc.1114C>T p.Leu372Leu synonymous_variant 9/25 ENST00000503335.7 NP_001243474.1 Q96KG7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MEGF10ENST00000503335.7 linkuse as main transcriptc.1114C>T p.Leu372Leu synonymous_variant 9/251 NM_001256545.2 ENSP00000423354.2 Q96KG7-1

Frequencies

GnomAD3 genomes
AF:
0.946
AC:
144063
AN:
152224
Hom.:
68260
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.986
Gnomad AMI
AF:
0.934
Gnomad AMR
AF:
0.959
Gnomad ASJ
AF:
0.958
Gnomad EAS
AF:
1.00
Gnomad SAS
AF:
0.967
Gnomad FIN
AF:
0.922
Gnomad MID
AF:
0.965
Gnomad NFE
AF:
0.917
Gnomad OTH
AF:
0.942
GnomAD3 exomes
AF:
0.944
AC:
230324
AN:
243864
Hom.:
108850
AF XY:
0.943
AC XY:
124506
AN XY:
132068
show subpopulations
Gnomad AFR exome
AF:
0.987
Gnomad AMR exome
AF:
0.967
Gnomad ASJ exome
AF:
0.950
Gnomad EAS exome
AF:
1.00
Gnomad SAS exome
AF:
0.964
Gnomad FIN exome
AF:
0.925
Gnomad NFE exome
AF:
0.920
Gnomad OTH exome
AF:
0.938
GnomAD4 exome
AF:
0.925
AC:
1345477
AN:
1454488
Hom.:
622695
Cov.:
45
AF XY:
0.926
AC XY:
670213
AN XY:
723514
show subpopulations
Gnomad4 AFR exome
AF:
0.987
Gnomad4 AMR exome
AF:
0.966
Gnomad4 ASJ exome
AF:
0.949
Gnomad4 EAS exome
AF:
1.00
Gnomad4 SAS exome
AF:
0.965
Gnomad4 FIN exome
AF:
0.925
Gnomad4 NFE exome
AF:
0.914
Gnomad4 OTH exome
AF:
0.936
GnomAD4 genome
AF:
0.946
AC:
144180
AN:
152342
Hom.:
68318
Cov.:
34
AF XY:
0.947
AC XY:
70546
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.986
Gnomad4 AMR
AF:
0.959
Gnomad4 ASJ
AF:
0.958
Gnomad4 EAS
AF:
1.00
Gnomad4 SAS
AF:
0.966
Gnomad4 FIN
AF:
0.922
Gnomad4 NFE
AF:
0.917
Gnomad4 OTH
AF:
0.943
Alfa
AF:
0.927
Hom.:
89838
Bravo
AF:
0.952
Asia WGS
AF:
0.984
AC:
3421
AN:
3478

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 submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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: 94% of total chromosomes in ExAC -
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, no assertion criteria providedclinical testingJoint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+-- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingGeneDxJan 05, 2016This 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. -
MEGF10-related myopathy Benign:3
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This 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 submitterclinical testingGenome-Nilou LabSep 05, 2021- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.64
CADD
Benign
5.5
DANN
Benign
0.86

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.

Other links and lift over

dbSNP: rs31483; hg19: chr5-126746277; API