rs10519937

Positions:

• chr5-127386161-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001256545.2(MEGF10):​c.413-10371C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 152,108 control chromosomes in the GnomAD database, including 2,625 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 0.18 (2625 hom., cov: 33)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.326

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.413-10371C>T		intron_variant		ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.413-10371C>T		intron_variant		1	NM_001256545.2	ENSP00000423354	P1
MEGF10	ENST00000274473.6	c.413-10371C>T		intron_variant		1		ENSP00000274473	P1
MEGF10	ENST00000418761.6	c.413-10371C>T		intron_variant		1		ENSP00000416284
MEGF10	ENST00000508365.5	c.413-10371C>T		intron_variant		1		ENSP00000423195

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27405 AN: 151990 Hom.: 2617 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.161

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

GnomAD4 genome AF: 0.180 AC: 27438 AN: 152108 Hom.: 2625 Cov.: 33 AF XY: 0.178 AC XY: 13272 AN XY: 74360

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.160

Alfa AF: 0.176 Hom.: 367

Bravo AF: 0.177

Asia WGS AF: 0.142 AC: 497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.24

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

Other links and lift over

dbSNP: rs10519937; hg19: chr5-126721853; COSMIC: COSV57250137;