dbSNP rs36061366: MEGF10:p.Asn919Asn (chr5-127447585-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_001256545.2(MEGF10):c.2757C>T(p.Asn919Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000921 in 1,614,116 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0045 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00054 ( 10 hom. )

Consequence

MEGF10
NM_001256545.2 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 0.131

Publications

0 publications found

Variant links:

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

MEGF10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 5-127447585-C-T is Benign according to our data. Variant chr5-127447585-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 384732.

BP7

Synonymous conserved (PhyloP=0.131 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00454 (692/152266) while in subpopulation AFR AF = 0.0154 (640/41544). AF 95% confidence interval is 0.0144. There are 6 homozygotes in GnomAd4. There are 327 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

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.2757C>T	p.Asn919Asn	synonymous	Exon 21 of 25	NP_001243474.1	Q96KG7-1
	MEGF10	NM_032446.3		c.2757C>T	p.Asn919Asn	synonymous	Exon 22 of 26	NP_115822.1	Q96KG7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEGF10	ENST00000503335.7	TSL:1 MANE Select	c.2757C>T	p.Asn919Asn	synonymous	Exon 21 of 25	ENSP00000423354.2	Q96KG7-1
MEGF10	ENST00000274473.6	TSL:1	c.2757C>T	p.Asn919Asn	synonymous	Exon 22 of 26	ENSP00000274473.6	Q96KG7-1
MEGF10	ENST00000507158.1	TSL:2	n.246C>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.00454

AC:

690

AN:

152148

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00119

AC:

298

AN:

251424

AF XY:

0.000890

show subpopulations

Gnomad AFR exome

AF:

0.0146

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000543

AC:

794

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000451

AC XY:

328

AN XY:

727216

show subpopulations

African (AFR)

AF:

0.0165

AC:

554

AN:

33478

American (AMR)

AF:

0.000961

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00139

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000656

AC:

AN:

1111980

Other (OTH)

AF:

0.00154

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

137

182

228

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00454

AC:

692

AN:

152266

Hom.:

Cov.:

AF XY:

0.00439

AC XY:

327

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0154

AC:

640

AN:

41544

American (AMR)

AF:

0.00209

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68008

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

129

161

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.00522

Asia WGS

AF:

0.00173

AC:

AN:

3478

EpiCase

AF:

0.000273

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

MEGF10-related myopathy (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.2

(source)

DANN

Benign

0.49

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over