5-127410427-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001256545.2(MEGF10):​c.956T>G​(p.Leu319Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

MEGF10
NM_001256545.2 missense

Scores

19

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.189
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 Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.07389945).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MEGF10NM_001256545.2 linkc.956T>G p.Leu319Arg missense_variant Exon 9 of 25 ENST00000503335.7 NP_001243474.1 Q96KG7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MEGF10ENST00000503335.7 linkc.956T>G p.Leu319Arg missense_variant Exon 9 of 25 1 NM_001256545.2 ENSP00000423354.2 Q96KG7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.036
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.63
CADD
Benign
2.0
DANN
Benign
0.51
DEOGEN2
Benign
0.019
T;.;.;T
Eigen
Benign
-1.4
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.038
N
LIST_S2
Benign
0.079
.;.;T;T
M_CAP
Benign
0.0080
T
MetaRNN
Benign
0.074
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
-0.47
N;N;N;N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
2.3
N;N;N;N
REVEL
Benign
0.0080
Sift
Benign
0.53
T;T;T;T
Sift4G
Benign
0.20
T;T;T;T
Polyphen
0.0
B;B;B;B
Vest4
0.17
MutPred
0.63
Gain of disorder (P = 0.0209);Gain of disorder (P = 0.0209);Gain of disorder (P = 0.0209);Gain of disorder (P = 0.0209);
MVP
0.043
MPC
0.32
ClinPred
0.061
T
GERP RS
0.15
Varity_R
0.052
gMVP
0.49

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-126746119; API