rs3812052

Variant names:

• chr5-127457282-T-A
• rs3812052
• NM_001256545.2:c.3387T>A

Your query was ambiguous. Multiple possible variants found:

• chr5-127457282-T-A
• chr5-127457282-T-C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001256545.2(MEGF10):​c.3387T>A​(p.Gly1129Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 1,613,440 control chromosomes in the GnomAD database, including 275,549 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (20146 hom., cov: 32)
  • Exomes 𝑓: 0.58 (255403 hom.)
• Consequence: MEGF10 NM_001256545.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -2.65
• Publications: 19 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, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 5-127457282-T-A is Benign according to our data. Variant chr5-127457282-T-A is described in ClinVar as Benign. ClinVar VariationId is 262076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.617 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEGF10	NM_001256545.2	MANE Select	c.3387T>A	p.Gly1129Gly	synonymous	Exon 25 of 25	NP_001243474.1	Q96KG7-1
	MEGF10	NM_032446.3		c.3387T>A	p.Gly1129Gly	synonymous	Exon 26 of 26	NP_115822.1	Q96KG7-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEGF10	ENST00000503335.7	TSL:1 MANE Select	c.3387T>A	p.Gly1129Gly	synonymous	Exon 25 of 25	ENSP00000423354.2	Q96KG7-1
	MEGF10	ENST00000274473.6	TSL:1	c.3387T>A	p.Gly1129Gly	synonymous	Exon 26 of 26	ENSP00000274473.6	Q96KG7-1
	MEGF10	ENST00000515622.1	TSL:2	n.433+1675T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73459 AN: 151854 Hom.: 20144 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.523

GnomAD2 exomes AF: 0.528 AC: 132339 AN: 250420 AF XY: 0.538

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.461

Gnomad ASJ exome AF: 0.601

Gnomad EAS exome AF: 0.294

Gnomad FIN exome AF: 0.601

Gnomad NFE exome AF: 0.624

Gnomad OTH exome AF: 0.574

GnomAD4 exome AF: 0.584 AC: 853559 AN: 1461468 Hom.: 255403 Cov.: 57 AF XY: 0.584 AC XY: 424335 AN XY: 727024

African (AFR) AF: 0.214 AC: 7162 AN: 33474

American (AMR) AF: 0.467 AC: 20861 AN: 44680

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 15900 AN: 26132

East Asian (EAS) AF: 0.292 AC: 11599 AN: 39690

South Asian (SAS) AF: 0.478 AC: 41173 AN: 86206

European-Finnish (FIN) AF: 0.602 AC: 32060 AN: 53294

Middle Eastern (MID) AF: 0.639 AC: 3684 AN: 5764

European-Non Finnish (NFE) AF: 0.618 AC: 687168 AN: 1111852

Other (OTH) AF: 0.562 AC: 33952 AN: 60376

GnomAD4 genome AF: 0.483 AC: 73466 AN: 151972 Hom.: 20146 Cov.: 32 AF XY: 0.483 AC XY: 35869 AN XY: 74292

African (AFR) AF: 0.226 AC: 9362 AN: 41432

American (AMR) AF: 0.505 AC: 7715 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2073 AN: 3470

East Asian (EAS) AF: 0.299 AC: 1540 AN: 5150

South Asian (SAS) AF: 0.446 AC: 2146 AN: 4816

European-Finnish (FIN) AF: 0.602 AC: 6359 AN: 10558

Middle Eastern (MID) AF: 0.663 AC: 195 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42274 AN: 67954

Other (OTH) AF: 0.527 AC: 1114 AN: 2114

Alfa AF: 0.585 Hom.: 8609

Bravo AF: 0.466

Asia WGS AF: 0.398 AC: 1383 AN: 3478

EpiCase AF: 0.633

EpiControl AF: 0.641

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	MEGF10-related myopathy (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.12
DANN	Benign	0.38
PhyloP100		-2.6
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: rs3812052; hg19: chr5-126792974; COSMIC: COSV57245128; COSMIC: COSV57245128;