rs34649270

Variant names:

• chr5-127396608-C-G
• NM_001256545.2:c.489C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-127396608-C-G
• chr5-127396608-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001256545.2(MEGF10):​c.489C>G​(p.Ile163Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MEGF10 NM_001256545.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.986

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.489C>G	p.Ile163Met	missense_variant	Exon 6 of 25	ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.489C>G	p.Ile163Met	missense_variant	Exon 6 of 25	1	NM_001256545.2	ENSP00000423354.2
MEGF10	ENST00000274473.6	c.489C>G	p.Ile163Met	missense_variant	Exon 7 of 26	1		ENSP00000274473.6
MEGF10	ENST00000418761.6	c.489C>G	p.Ile163Met	missense_variant	Exon 7 of 15	1		ENSP00000416284.2
MEGF10	ENST00000508365.5	c.489C>G	p.Ile163Met	missense_variant	Exon 6 of 14	1		ENSP00000423195.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T;.;.;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.85	.;.;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.63	D;D;D;D
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L;L;L;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.72	N;N;N;N
REVEL	Benign	0.23
Sift	Benign	0.030	D;D;D;D
Sift4G	Uncertain	0.034	D;D;D;D
Polyphen		1.0	D;P;P;D
Vest4		0.71
MutPred		0.59		Gain of disorder (P = 0.0226);Gain of disorder (P = 0.0226);Gain of disorder (P = 0.0226);Gain of disorder (P = 0.0226);
MVP		0.28
MPC		0.84
ClinPred		0.70	D
GERP RS		4.7
Varity_R		0.15
gMVP		0.21

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: chr5-126732300;