chr5-127398673-C-T

Position:

chr5-127398673-C-T

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The ENST00000503335.7(MEGF10):c.660-3C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.157 in 1,613,692 control chromosomes in the GnomAD database, including 21,498 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 3348 hom., cov: 32)

Exomes 𝑓: 0.15 ( 18150 hom. )

Consequence

MEGF10
ENST00000503335.7 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.003024

Clinical Significance

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

Conservation

PhyloP100: 1.97

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 -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BP6

Variant 5-127398673-C-T is Benign according to our data. Variant chr5-127398673-C-T is described in ClinVar as [Benign]. Clinvar id is 262080.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.313 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.660-3C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7 linkuse as main transcript	c.660-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1	NM_001256545.2	ENSP00000423354	P1	Q96KG7-1
MEGF10	ENST00000274473.6 linkuse as main transcript	c.660-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000274473	P1	Q96KG7-1
MEGF10	ENST00000418761.6 linkuse as main transcript	c.660-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000416284		Q96KG7-2
MEGF10	ENST00000508365.5 linkuse as main transcript	c.660-3C>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000423195		Q96KG7-2

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29378

AN:

152056

Hom.:

3333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.0614

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.153

Gnomad EAS

AF:

0.106

Gnomad SAS

AF:

0.194

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.150

Gnomad OTH

AF:

0.169

GnomAD3 exomes

AF:

0.153

AC:

38556

AN:

251306

Hom.:

3388

AF XY:

0.153

AC XY:

20769

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.322

Gnomad AMR exome

AF:

0.0873

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.0985

Gnomad SAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.165

Gnomad NFE exome

AF:

0.153

Gnomad OTH exome

AF:

0.148

GnomAD4 exome

AF:

0.154

AC:

224672

AN:

1461520

Hom.:

18150

Cov.:

AF XY:

0.153

AC XY:

111256

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.317

Gnomad4 AMR exome

AF:

0.0894

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.110

Gnomad4 SAS exome

AF:

0.169

Gnomad4 FIN exome

AF:

0.170

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.151

GnomAD4 genome

AF:

0.193

AC:

29422

AN:

152172

Hom.:

3348

Cov.:

AF XY:

0.191

AC XY:

14233

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.317

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.153

Gnomad4 EAS

AF:

0.106

Gnomad4 SAS

AF:

0.194

Gnomad4 FIN

AF:

0.163

Gnomad4 NFE

AF:

0.150

Gnomad4 OTH

AF:

0.168

Alfa

AF:

0.171

Hom.:

1356

Bravo

AF:

0.194

Asia WGS

AF:

0.139

AC:

488

AN:

3478

EpiCase

AF:

0.136

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	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	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	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

-0.22

CADD

Benign

DANN

Benign

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0030

dbscSNV1_RF

Benign

0.12

SpliceAI score (max)

0.020

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