rs56157640

Variant names:

• chr5-127455564-G-A
• rs56157640
• NM_001256545.2:c.3189G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-127455564-G-A
• chr5-127455564-G-T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001256545.2(MEGF10):​c.3189G>A​(p.Glu1063Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0215 in 1,614,078 control chromosomes in the GnomAD database, including 602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.019 (54 hom., cov: 32)
  • Exomes 𝑓: 0.022 (548 hom.)
• Consequence: MEGF10 NM_001256545.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.59
• Publications: 3 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: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 5-127455564-G-A is Benign according to our data. Variant chr5-127455564-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 380909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.59 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0713 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.3189G>A	p.Glu1063Glu	synonymous	Exon 24 of 25	NP_001243474.1	Q96KG7-1
	MEGF10	NM_032446.3		c.3189G>A	p.Glu1063Glu	synonymous	Exon 25 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.3189G>A	p.Glu1063Glu	synonymous	Exon 24 of 25	ENSP00000423354.2	Q96KG7-1
	MEGF10	ENST00000274473.6	TSL:1	c.3189G>A	p.Glu1063Glu	synonymous	Exon 25 of 26	ENSP00000274473.6	Q96KG7-1
	MEGF10	ENST00000515622.1	TSL:2	n.390G>A		non_coding_transcript_exon	Exon 4 of 5

Frequencies

GnomAD3 genomes AF: 0.0187 AC: 2849 AN: 152136 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.00674

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.0500

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0174

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.0266 AC: 6667 AN: 251088 AF XY: 0.0291

Gnomad AFR exome AF: 0.00517

Gnomad AMR exome AF: 0.0111

Gnomad ASJ exome AF: 0.0466

Gnomad EAS exome AF: 0.0500

Gnomad FIN exome AF: 0.0293

Gnomad NFE exome AF: 0.0175

Gnomad OTH exome AF: 0.0262

GnomAD4 exome AF: 0.0218 AC: 31891 AN: 1461824 Hom.: 548 Cov.: 31 AF XY: 0.0231 AC XY: 16829 AN XY: 727218

African (AFR) AF: 0.00511 AC: 171 AN: 33480

American (AMR) AF: 0.0105 AC: 469 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0454 AC: 1187 AN: 26132

East Asian (EAS) AF: 0.0387 AC: 1537 AN: 39684

South Asian (SAS) AF: 0.0661 AC: 5704 AN: 86254

European-Finnish (FIN) AF: 0.0293 AC: 1567 AN: 53416

Middle Eastern (MID) AF: 0.0260 AC: 150 AN: 5768

European-Non Finnish (NFE) AF: 0.0176 AC: 19582 AN: 1111976

Other (OTH) AF: 0.0252 AC: 1524 AN: 60394

GnomAD4 genome AF: 0.0187 AC: 2846 AN: 152254 Hom.: 54 Cov.: 32 AF XY: 0.0206 AC XY: 1530 AN XY: 74442

African (AFR) AF: 0.00672 AC: 279 AN: 41538

American (AMR) AF: 0.0108 AC: 165 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0476 AC: 165 AN: 3466

East Asian (EAS) AF: 0.0500 AC: 259 AN: 5184

South Asian (SAS) AF: 0.0777 AC: 375 AN: 4824

European-Finnish (FIN) AF: 0.0313 AC: 331 AN: 10592

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0174 AC: 1187 AN: 68028

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0187 Hom.: 18

Bravo AF: 0.0153

Asia WGS AF: 0.0500 AC: 173 AN: 3478

EpiCase AF: 0.0182

EpiControl AF: 0.0156

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	MEGF10-related myopathy (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	5.5
DANN	Benign	0.47
PhyloP100		1.6
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: rs56157640; hg19: chr5-126791256;