chr5-127434831-G-A

Position:

chr5-127434831-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001256545.2(MEGF10):c.1975+10G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000574 in 1,610,420 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00075 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 3 hom. )

Consequence

MEGF10
NM_001256545.2 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: -1.46

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 5-127434831-G-A is Benign according to our data. Variant chr5-127434831-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 511785.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF10	NM_001256545.2 linkuse as main transcript	c.1975+10G>A		intron_variant		ENST00000503335.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
MEGF10	ENST00000503335.7 linkuse as main transcript	c.1975+10G>A	intron_variant	1	NM_001256545.2	P1	Q96KG7-1
MEGF10	ENST00000274473.6 linkuse as main transcript	c.1975+10G>A	intron_variant	1		P1	Q96KG7-1
MEGF10	ENST00000506709.1 linkuse as main transcript	n.216+10G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.000749

AC:

114

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000823

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000683

AC:

168

AN:

246140

Hom.:

AF XY:

0.000705

AC XY:

AN XY:

133280

show subpopulations

Gnomad AFR exome

AF:

0.000495

Gnomad AMR exome

AF:

0.0000291

Gnomad ASJ exome

AF:

0.00839

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000254

Gnomad NFE exome

AF:

0.000620

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000555

AC:

810

AN:

1458152

Hom.:

Cov.:

AF XY:

0.000515

AC XY:

374

AN XY:

725514

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.0100

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000983

Gnomad4 NFE exome

AF:

0.000434

Gnomad4 OTH exome

AF:

0.000812

GnomAD4 genome

AF:

0.000749

AC:

114

AN:

152268

Hom.:

Cov.:

AF XY:

0.000685

AC XY:

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000823

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00113

Hom.:

Bravo

AF:

0.000725

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

MEGF10-related myopathy

Uncertain:1Benign:1

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 06, 2024	- -
Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

MEGF10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 30, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.046

DANN

Benign

0.50

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