Genetic Variant MEGF10:c.-18-11C>A (chr5-127331280-C-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS1

The NM_001256545.2(MEGF10):c.-18-11C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000071 in 1,408,020 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000032 ( 0 hom. )

Consequence

MEGF10
NM_001256545.2 intron

Scores

Splicing: ADA: 0.0005358

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen

MEGF10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS1

Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0000395 (6/151992) while in subpopulation AMR AF = 0.000393 (6/15260). AF 95% confidence interval is 0.00017. There are 0 homozygotes in GnomAd4. There are 3 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF10	NM_001256545.2 link	c.-18-11C>A		intron_variant	Intron 1 of 24	ENST00000503335.7	NP_001243474.1	Q96KG7-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MEGF10	ENST00000503335.7 link	c.-18-11C>A	intron_variant	Intron 1 of 24	1	NM_001256545.2	ENSP00000423354.2	Q96KG7-1
MEGF10	ENST00000274473.6 link	c.-18-11C>A	intron_variant	Intron 2 of 25	1		ENSP00000274473.6	Q96KG7-1
MEGF10	ENST00000418761.6 link	c.-18-11C>A	intron_variant	Intron 2 of 14	1		ENSP00000416284.2	Q96KG7-2
MEGF10	ENST00000508365.5 link	c.-18-11C>A	intron_variant	Intron 1 of 13	1		ENSP00000423195.1	Q96KG7-2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151992

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000169

AC:

AN:

237108

AF XY:

0.0000234

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000318

AC:

AN:

1256028

Hom.:

Cov.:

AF XY:

0.00000472

AC XY:

AN XY:

635158

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28556

American (AMR)

AF:

0.0000976

AC:

AN:

40978

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24266

East Asian (EAS)

AF:

0.00

AC:

AN:

38644

South Asian (SAS)

AF:

0.00

AC:

AN:

80050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52904

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

932110

Other (OTH)

AF:

0.00

AC:

AN:

53210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.538

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151992

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41354

American (AMR)

AF:

0.000393

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67978

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

9.2

(source)

DANN

Benign

0.13

PhyloP100

0.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00054

dbscSNV1_RF

Benign

0.24

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over