rs35525

Variant names:

• chr5-127363655-G-A
• rs35525
• NM_001256545.2:c.320-6255G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-127363655-G-A
• chr5-127363655-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.84).
• 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 rank	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.320-6255G>A		intron_variant	Intron 4 of 24	ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.320-6255G>A		intron_variant	Intron 4 of 24	1	NM_001256545.2	ENSP00000423354.2
MEGF10	ENST00000274473.6	c.320-6255G>A		intron_variant	Intron 5 of 25	1		ENSP00000274473.6
MEGF10	ENST00000418761.6	c.320-6255G>A		intron_variant	Intron 5 of 14	1		ENSP00000416284.2
MEGF10	ENST00000508365.5	c.320-6255G>A		intron_variant	Intron 4 of 13	1		ENSP00000423195.1

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

African (AFR) AF: 0.492 AC: 20394 AN: 41436

American (AMR) AF: 0.444 AC: 6774 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1768 AN: 3472

East Asian (EAS) AF: 0.374 AC: 1937 AN: 5174

South Asian (SAS) AF: 0.477 AC: 2300 AN: 4824

European-Finnish (FIN) AF: 0.466 AC: 4912 AN: 10548

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34687 AN: 67962

Other (OTH) AF: 0.509 AC: 1075 AN: 2110

Alfa AF: 0.498 Hom.: 22681

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
PhyloP100		0.11
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: rs35525; hg19: chr5-126699347; COSMIC: COSV57246968;