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GeneBe

chr5-127339238-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001256545.2(MEGF10):​c.218+17C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00347 in 1,569,170 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0036 ( 18 hom. )

Consequence

MEGF10
NM_001256545.2 intron

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.231
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
Variant 5-127339238-C-G is Benign according to our data. Variant chr5-127339238-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 262070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00247 (376/152120) while in subpopulation NFE AF= 0.0038 (258/67984). AF 95% confidence interval is 0.00341. There are 1 homozygotes in gnomad4. There are 186 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MEGF10NM_001256545.2 linkuse as main transcriptc.218+17C>G intron_variant ENST00000503335.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MEGF10ENST00000503335.7 linkuse as main transcriptc.218+17C>G intron_variant 1 NM_001256545.2 P1Q96KG7-1
MEGF10ENST00000274473.6 linkuse as main transcriptc.218+17C>G intron_variant 1 P1Q96KG7-1
MEGF10ENST00000418761.6 linkuse as main transcriptc.218+17C>G intron_variant 1 Q96KG7-2
MEGF10ENST00000508365.5 linkuse as main transcriptc.218+17C>G intron_variant 1 Q96KG7-2

Frequencies

GnomAD3 genomes
AF:
0.00247
AC:
376
AN:
152002
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00101
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00322
Gnomad ASJ
AF:
0.00432
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000283
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00379
Gnomad OTH
AF:
0.00430
GnomAD3 exomes
AF:
0.00232
AC:
575
AN:
247516
Hom.:
2
AF XY:
0.00224
AC XY:
300
AN XY:
133704
show subpopulations
Gnomad AFR exome
AF:
0.000927
Gnomad AMR exome
AF:
0.00181
Gnomad ASJ exome
AF:
0.00453
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000699
Gnomad NFE exome
AF:
0.00373
Gnomad OTH exome
AF:
0.00350
GnomAD4 exome
AF:
0.00358
AC:
5069
AN:
1417050
Hom.:
18
Cov.:
23
AF XY:
0.00340
AC XY:
2405
AN XY:
707404
show subpopulations
Gnomad4 AFR exome
AF:
0.000524
Gnomad4 AMR exome
AF:
0.00199
Gnomad4 ASJ exome
AF:
0.00444
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000563
Gnomad4 NFE exome
AF:
0.00428
Gnomad4 OTH exome
AF:
0.00376
GnomAD4 genome
AF:
0.00247
AC:
376
AN:
152120
Hom.:
1
Cov.:
32
AF XY:
0.00250
AC XY:
186
AN XY:
74366
show subpopulations
Gnomad4 AFR
AF:
0.00101
Gnomad4 AMR
AF:
0.00321
Gnomad4 ASJ
AF:
0.00432
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000283
Gnomad4 NFE
AF:
0.00380
Gnomad4 OTH
AF:
0.00425
Alfa
AF:
0.00294
Hom.:
1
Bravo
AF:
0.00267
Asia WGS
AF:
0.000289
AC:
2
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

MEGF10-related myopathy Benign:3
Benign, criteria provided, single submitterclinical testingInvitaeJan 25, 2024- -
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsOct 21, 2021- -
Benign, criteria provided, single submitterclinical testingCentre for Mendelian Genomics, University Medical Centre LjubljanaOct 31, 2018This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. -
not specified Benign:2
Likely benign, criteria provided, single submitterclinical testingGeneDxAug 02, 2017This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.28
DANN
Benign
0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs72786483; hg19: chr5-126674930; API