5-127410517-G-C

Variant names:

• chr5-127410517-G-C
• NM_001256545.2:c.1046G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001256545.2(MEGF10):​c.1046G>C​(p.Arg349Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: MEGF10 NM_001256545.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3010077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.1046G>C	p.Arg349Pro	missense_variant	Exon 9 of 25	ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.1046G>C	p.Arg349Pro	missense_variant	Exon 9 of 25	1	NM_001256545.2	ENSP00000423354.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461494 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	0.95
DANN	Uncertain	0.98
DEOGEN2	Benign	0.19	T;.;.;T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.14	N
LIST_S2	Uncertain	0.91	.;.;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.30	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Pathogenic	3.0	M;M;M;M
PrimateAI	Benign	0.26	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Benign	0.12
Sift	Benign	0.041	D;D;D;D
Sift4G	Benign	0.14	T;T;T;T
Polyphen		0.28	B;B;B;B
Vest4		0.40
MutPred		0.62		Gain of catalytic residue at R349 (P = 0.0514);Gain of catalytic residue at R349 (P = 0.0514);Gain of catalytic residue at R349 (P = 0.0514);Gain of catalytic residue at R349 (P = 0.0514);
MVP		0.31
MPC		0.44
ClinPred		0.33	T
GERP RS		-4.7
Varity_R		0.31
gMVP		0.67

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: chr5-126746209;