rs375276332
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_001256545.2(MEGF10):āc.365A>Gā(p.Asn122Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000589 in 1,612,906 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 (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.000061 ( 0 hom. )
Consequence
MEGF10
NM_001256545.2 missense
NM_001256545.2 missense
Scores
1
6
11
Clinical Significance
Conservation
PhyloP100: 7.37
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.034740597).
BP6
?
Variant 5-127369955-A-G is Benign according to our data. Variant chr5-127369955-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 579510.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MEGF10 | NM_001256545.2 | c.365A>G | p.Asn122Ser | missense_variant | 5/25 | ENST00000503335.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MEGF10 | ENST00000503335.7 | c.365A>G | p.Asn122Ser | missense_variant | 5/25 | 1 | NM_001256545.2 | P1 | |
MEGF10 | ENST00000274473.6 | c.365A>G | p.Asn122Ser | missense_variant | 6/26 | 1 | P1 | ||
MEGF10 | ENST00000418761.6 | c.365A>G | p.Asn122Ser | missense_variant | 6/15 | 1 | |||
MEGF10 | ENST00000508365.5 | c.365A>G | p.Asn122Ser | missense_variant | 5/14 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151994Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
6
AN:
151994
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000152 AC: 38AN: 250750Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135548
GnomAD3 exomes
AF:
AC:
38
AN:
250750
Hom.:
AF XY:
AC XY:
17
AN XY:
135548
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000609 AC: 89AN: 1460912Hom.: 0 Cov.: 30 AF XY: 0.0000440 AC XY: 32AN XY: 726782
GnomAD4 exome
AF:
AC:
89
AN:
1460912
Hom.:
Cov.:
30
AF XY:
AC XY:
32
AN XY:
726782
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151994Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74226
GnomAD4 genome
?
AF:
AC:
6
AN:
151994
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74226
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
?
AF:
AC:
20
Asia WGS
AF:
AC:
11
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
MEGF10-related myopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 06, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M;M;M
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Benign
T;T;T;T
Polyphen
P;P;P;P
Vest4
MVP
MPC
0.71
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at