rs200994008
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001256545.2(MEGF10):c.2145G>A(p.Thr715=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,614,112 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000020 ( 0 hom. )
Consequence
MEGF10
NM_001256545.2 synonymous
NM_001256545.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -4.25
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
?
Variant 5-127438479-G-A is Benign according to our data. Variant chr5-127438479-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 262069.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-4.24 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF10 | NM_001256545.2 | c.2145G>A | p.Thr715= | synonymous_variant | 17/25 | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.2145G>A | p.Thr715= | synonymous_variant | 17/25 | 1 | NM_001256545.2 | P1 | |
MEGF10 | ENST00000274473.6 | c.2145G>A | p.Thr715= | synonymous_variant | 18/26 | 1 | P1 | ||
MEGF10 | ENST00000506709.1 | n.386G>A | non_coding_transcript_exon_variant | 4/5 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152150Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000321 AC: 8AN: 249226Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134900
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GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461844Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 727224
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GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152268Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74458
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
MEGF10-related myopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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