5-127321525-G-T

Variant names:

• chr5-127321525-G-T
• rs152121
• NM_001256545.2:c.-18-9766G>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.-18-9766G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 151,902 control chromosomes in the GnomAD database, including 18,000 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 0.47 (18000 hom., cov: 31)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.-18-9766G>T		intron_variant	Intron 1 of 24	ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.-18-9766G>T		intron_variant	Intron 1 of 24	1	NM_001256545.2	ENSP00000423354.2
MEGF10	ENST00000274473.6	c.-18-9766G>T		intron_variant	Intron 2 of 25	1		ENSP00000274473.6
MEGF10	ENST00000418761.6	c.-18-9766G>T		intron_variant	Intron 2 of 14	1		ENSP00000416284.2
MEGF10	ENST00000508365.5	c.-18-9766G>T		intron_variant	Intron 1 of 13	1		ENSP00000423195.1

Frequencies

GnomAD3 genomes AF: 0.473 AC: 71754 AN: 151784 Hom.: 17990 Cov.: 31

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.456

Gnomad ASJ AF: 0.498

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.473 AC: 71783 AN: 151902 Hom.: 18000 Cov.: 31 AF XY: 0.467 AC XY: 34655 AN XY: 74240

African (AFR) AF: 0.326 AC: 13504 AN: 41416

American (AMR) AF: 0.455 AC: 6939 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.498 AC: 1727 AN: 3468

East Asian (EAS) AF: 0.283 AC: 1459 AN: 5154

South Asian (SAS) AF: 0.418 AC: 2009 AN: 4810

European-Finnish (FIN) AF: 0.492 AC: 5194 AN: 10558

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 38992 AN: 67928

Other (OTH) AF: 0.494 AC: 1044 AN: 2112

Alfa AF: 0.504 Hom.: 6370

Bravo AF: 0.462

Asia WGS AF: 0.378 AC: 1316 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	0.25
DANN	Benign	0.59
PhyloP100		-1.0
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: rs152121; hg19: chr5-126657217; COSMIC: COSV57246804;