5-127363655-G-A

Position:

• chr5-127363655-G-A

Variant summary

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

The NM_001256545.2(MEGF10):​c.320-6255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.492 in 152,000 control chromosomes in the GnomAD database, including 18,547 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 0.49 (18547 hom., cov: 32)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.107

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.320-6255G>A		intron_variant		ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.320-6255G>A		intron_variant		1	NM_001256545.2	ENSP00000423354	P1
MEGF10	ENST00000274473.6	c.320-6255G>A		intron_variant		1		ENSP00000274473	P1
MEGF10	ENST00000418761.6	c.320-6255G>A		intron_variant		1		ENSP00000416284
MEGF10	ENST00000508365.5	c.320-6255G>A		intron_variant		1		ENSP00000423195

Frequencies

GnomAD3 genomes AF: 0.491 AC: 74647 AN: 151882 Hom.: 18520 Cov.: 32

Gnomad AFR AF: 0.492

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.492 AC: 74710 AN: 152000 Hom.: 18547 Cov.: 32 AF XY: 0.487 AC XY: 36218 AN XY: 74294

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.509

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.477

Gnomad4 FIN AF: 0.466

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.509

Alfa AF: 0.499 Hom.: 17002

Bravo AF: 0.489

Asia WGS AF: 0.446 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.52
DANN	Benign	0.82

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: rs35525; hg19: chr5-126699347; COSMIC: COSV57246968;