rs17684740

Variant names:

• chr5-127384723-T-C
• rs17684740
• NM_001256545.2:c.413-11809T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256545.2(MEGF10):​c.413-11809T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,326 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.019 (52 hom., cov: 33)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• MEGF10-related myopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256545.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEGF10	NM_001256545.2	MANE Select	c.413-11809T>C		intron	N/A	NP_001243474.1
	MEGF10	NM_032446.3		c.413-11809T>C		intron	N/A	NP_115822.1
	MEGF10	NM_001308119.2		c.413-11809T>C		intron	N/A	NP_001295048.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEGF10	ENST00000503335.7	TSL:1 MANE Select	c.413-11809T>C		intron	N/A	ENSP00000423354.2
	MEGF10	ENST00000274473.6	TSL:1	c.413-11809T>C		intron	N/A	ENSP00000274473.6
	MEGF10	ENST00000418761.6	TSL:1	c.413-11809T>C		intron	N/A	ENSP00000416284.2

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2921 AN: 152208 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0187

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0192 AC: 2920 AN: 152326 Hom.: 52 Cov.: 33 AF XY: 0.0205 AC XY: 1527 AN XY: 74498

African (AFR) AF: 0.0164 AC: 681 AN: 41570

American (AMR) AF: 0.0114 AC: 175 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0470 AC: 163 AN: 3468

East Asian (EAS) AF: 0.0469 AC: 243 AN: 5184

South Asian (SAS) AF: 0.0758 AC: 366 AN: 4826

European-Finnish (FIN) AF: 0.0215 AC: 228 AN: 10624

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0145 AC: 986 AN: 68034

Other (OTH) AF: 0.0180 AC: 38 AN: 2112

Alfa AF: 0.0156 Hom.: 1

Bravo AF: 0.0171

Asia WGS AF: 0.0500 AC: 174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.46
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17684740; hg19: chr5-126720415;