rs17164938

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001256545.2(MEGF10):c.3162G>A(p.Pro1054=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 1,613,852 control chromosomes in the GnomAD database, including 914 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 82 hom., cov: 32)

Exomes 𝑓: 0.032 ( 832 hom. )

Consequence

MEGF10
NM_001256545.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.53

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=-0.71).

BP6

Variant 5-127455537-G-A is Benign according to our data. Variant chr5-127455537-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262074.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.53 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0324 (4932/152138) while in subpopulation EAS AF= 0.045 (232/5158). AF 95% confidence interval is 0.0402. There are 82 homozygotes in gnomad4. There are 2273 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 82 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF10	NM_001256545.2 linkuse as main transcript	c.3162G>A	p.Pro1054=	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.3162G>A	p.Pro1054=	synonymous_variant	24/25	1	NM_001256545.2	ENSP00000423354	P1	Q96KG7-1
MEGF10	ENST00000274473.6 linkuse as main transcript	c.3162G>A	p.Pro1054=	synonymous_variant	25/26	1		ENSP00000274473	P1	Q96KG7-1
MEGF10	ENST00000510828.5 linkuse as main transcript	n.661G>A		non_coding_transcript_exon_variant	6/6	5
MEGF10	ENST00000515622.1 linkuse as main transcript	n.363G>A		non_coding_transcript_exon_variant	4/5	2

Frequencies

GnomAD3 genomes

AF:

0.0324

AC:

4925

AN:

152020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0410

Gnomad AMI

AF:

0.00548

Gnomad AMR

AF:

0.0272

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.0449

Gnomad SAS

AF:

0.0124

Gnomad FIN

AF:

0.0192

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0319

Gnomad OTH

AF:

0.0326

GnomAD3 exomes

AF:

0.0277

AC:

6946

AN:

251148

Hom.:

124

AF XY:

0.0272

AC XY:

3693

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.0381

Gnomad AMR exome

AF:

0.0207

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.0449

Gnomad SAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.0207

Gnomad NFE exome

AF:

0.0311

Gnomad OTH exome

AF:

0.0276

GnomAD4 exome

AF:

0.0319

AC:

46669

AN:

1461714

Hom.:

832

Cov.:

AF XY:

0.0312

AC XY:

22721

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.0395

Gnomad4 AMR exome

AF:

0.0210

Gnomad4 ASJ exome

AF:

0.0165

Gnomad4 EAS exome

AF:

0.0373

Gnomad4 SAS exome

AF:

0.0138

Gnomad4 FIN exome

AF:

0.0224

Gnomad4 NFE exome

AF:

0.0340

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0324

AC:

4932

AN:

152138

Hom.:

Cov.:

AF XY:

0.0306

AC XY:

2273

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0412

Gnomad4 AMR

AF:

0.0271

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.0450

Gnomad4 SAS

AF:

0.0125

Gnomad4 FIN

AF:

0.0192

Gnomad4 NFE

AF:

0.0319

Gnomad4 OTH

AF:

0.0318

Alfa

AF:

0.0287

Hom.:

102

Bravo

AF:

0.0343

Asia WGS

AF:

0.0280

AC:

AN:

3478

EpiCase

AF:

0.0313

EpiControl

AF:

0.0290

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	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 28, 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. -

MEGF10-related myopathy

Benign:2

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

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

-0.71

CADD

Benign

0.78

DANN

Benign

0.54

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