rs538399152
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_001256545.2(MEGF10):c.117-5_117-4insC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000507 in 1,567,582 control chromosomes in the GnomAD database, including 10 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0010 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00045 ( 8 hom. )
Consequence
MEGF10
NM_001256545.2 splice_region, intron
NM_001256545.2 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.380
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 -9 ACMG points.
BP6
Variant 5-127339115-T-TC is Benign according to our data. Variant chr5-127339115-T-TC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 350635.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=2}.
BS1
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00102 (156/152234) while in subpopulation EAS AF= 0.0272 (141/5184). AF 95% confidence interval is 0.0235. There are 2 homozygotes in gnomad4. There are 76 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MEGF10 | NM_001256545.2 | c.117-5_117-4insC | splice_region_variant, intron_variant | ENST00000503335.7 | NP_001243474.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.117-5_117-4insC | splice_region_variant, intron_variant | 1 | NM_001256545.2 | ENSP00000423354.2 | ||||
MEGF10 | ENST00000274473.6 | c.117-5_117-4insC | splice_region_variant, intron_variant | 1 | ENSP00000274473.6 | |||||
MEGF10 | ENST00000418761.6 | c.117-5_117-4insC | splice_region_variant, intron_variant | 1 | ENSP00000416284.2 | |||||
MEGF10 | ENST00000508365.5 | c.117-5_117-4insC | splice_region_variant, intron_variant | 1 | ENSP00000423195.1 |
Frequencies
GnomAD3 genomes AF: 0.00102 AC: 155AN: 152116Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.00170 AC: 411AN: 241680Hom.: 6 AF XY: 0.00155 AC XY: 202AN XY: 130584
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GnomAD4 exome AF: 0.000451 AC: 638AN: 1415348Hom.: 8 Cov.: 25 AF XY: 0.000425 AC XY: 300AN XY: 705060
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GnomAD4 genome AF: 0.00102 AC: 156AN: 152234Hom.: 2 Cov.: 32 AF XY: 0.00102 AC XY: 76AN XY: 74426
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
MEGF10-related myopathy Uncertain:1Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 26, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 18, 2018 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at