5-127418618-C-G

Variant names:

• chr5-127418618-C-G
• rs1990955
• NM_001256545.2:c.1306-502C>G

Variant summary

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

The NM_001256545.2(MEGF10):​c.1306-502C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 152,258 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 0.021 (52 hom., cov: 32)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.146
• Publications: 0 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0665 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.1306-502C>G		intron	N/A	NP_001243474.1
	MEGF10	NM_032446.3		c.1306-502C>G		intron	N/A	NP_115822.1
	MEGF10	NM_001308119.2		c.1306-502C>G		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.1306-502C>G		intron	N/A	ENSP00000423354.2
	MEGF10	ENST00000274473.6	TSL:1	c.1306-502C>G		intron	N/A	ENSP00000274473.6
	MEGF10	ENST00000418761.6	TSL:1	c.1306-502C>G		intron	N/A	ENSP00000416284.2

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3161 AN: 152140 Hom.: 51 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.0726

Gnomad FIN AF: 0.0317

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0173

Gnomad OTH AF: 0.0215

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

GnomAD4 genome AF: 0.0207 AC: 3157 AN: 152258 Hom.: 52 Cov.: 32 AF XY: 0.0223 AC XY: 1662 AN XY: 74442

African (AFR) AF: 0.0146 AC: 606 AN: 41550

American (AMR) AF: 0.0114 AC: 175 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3468

East Asian (EAS) AF: 0.0499 AC: 259 AN: 5186

South Asian (SAS) AF: 0.0728 AC: 351 AN: 4820

European-Finnish (FIN) AF: 0.0317 AC: 336 AN: 10606

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0173 AC: 1180 AN: 68012

Other (OTH) AF: 0.0208 AC: 44 AN: 2112

Alfa AF: 0.00542 Hom.: 1

Bravo AF: 0.0179

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.93
DANN	Benign	0.60
PhyloP100		-0.15
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: rs1990955; hg19: chr5-126754310;