rs31483

Variant names:

• chr5-127410585-C-T
• rs31483
• NM_001256545.2:c.1114C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-127410585-C-T
• chr5-127410585-C-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001256545.2(MEGF10):​c.1114C>T​(p.Leu372Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 1,606,830 control chromosomes in the GnomAD database, including 691,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68318 hom., cov: 34)
  • Exomes 𝑓: 0.93 (622695 hom.)
• Consequence: MEGF10 NM_001256545.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.168
• Publications: 15 publications found

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]

MEGF10 Gene-Disease associations (from GenCC):

• MEGF10-related myopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 5-127410585-C-T is Benign according to our data. Variant chr5-127410585-C-T is described in ClinVar as Benign. ClinVar VariationId is 262060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.168 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.978 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256545.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEGF10	NM_001256545.2	MANE Select	c.1114C>T	p.Leu372Leu	synonymous	Exon 9 of 25	NP_001243474.1	Q96KG7-1
	MEGF10	NM_032446.3		c.1114C>T	p.Leu372Leu	synonymous	Exon 10 of 26	NP_115822.1	Q96KG7-1
	MEGF10	NM_001308119.2		c.1114C>T	p.Leu372Leu	synonymous	Exon 10 of 15	NP_001295048.1	Q96KG7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEGF10	ENST00000503335.7	TSL:1 MANE Select	c.1114C>T	p.Leu372Leu	synonymous	Exon 9 of 25	ENSP00000423354.2	Q96KG7-1
	MEGF10	ENST00000274473.6	TSL:1	c.1114C>T	p.Leu372Leu	synonymous	Exon 10 of 26	ENSP00000274473.6	Q96KG7-1
	MEGF10	ENST00000418761.6	TSL:1	c.1114C>T	p.Leu372Leu	synonymous	Exon 10 of 15	ENSP00000416284.2	Q96KG7-2

Frequencies

GnomAD3 genomes AF: 0.946 AC: 144063 AN: 152224 Hom.: 68260 Cov.: 34

Gnomad AFR AF: 0.986

Gnomad AMI AF: 0.934

Gnomad AMR AF: 0.959

Gnomad ASJ AF: 0.958

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.967

Gnomad FIN AF: 0.922

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.942

GnomAD2 exomes AF: 0.944 AC: 230324 AN: 243864 AF XY: 0.943

Gnomad AFR exome AF: 0.987

Gnomad AMR exome AF: 0.967

Gnomad ASJ exome AF: 0.950

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.925

Gnomad NFE exome AF: 0.920

Gnomad OTH exome AF: 0.938

GnomAD4 exome AF: 0.925 AC: 1345477 AN: 1454488 Hom.: 622695 Cov.: 45 AF XY: 0.926 AC XY: 670213 AN XY: 723514

African (AFR) AF: 0.987 AC: 33001 AN: 33442

American (AMR) AF: 0.966 AC: 43014 AN: 44536

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 24779 AN: 26110

East Asian (EAS) AF: 1.00 AC: 39659 AN: 39668

South Asian (SAS) AF: 0.965 AC: 82887 AN: 85882

European-Finnish (FIN) AF: 0.925 AC: 44251 AN: 47834

Middle Eastern (MID) AF: 0.959 AC: 5458 AN: 5690

European-Non Finnish (NFE) AF: 0.914 AC: 1016037 AN: 1111070

Other (OTH) AF: 0.936 AC: 56391 AN: 60256

GnomAD4 genome AF: 0.946 AC: 144180 AN: 152342 Hom.: 68318 Cov.: 34 AF XY: 0.947 AC XY: 70546 AN XY: 74494

African (AFR) AF: 0.986 AC: 41026 AN: 41592

American (AMR) AF: 0.959 AC: 14677 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.958 AC: 3325 AN: 3470

East Asian (EAS) AF: 1.00 AC: 5175 AN: 5176

South Asian (SAS) AF: 0.966 AC: 4668 AN: 4830

European-Finnish (FIN) AF: 0.922 AC: 9800 AN: 10624

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62380 AN: 68020

Other (OTH) AF: 0.943 AC: 1993 AN: 2114

Alfa AF: 0.931 Hom.: 124238

Bravo AF: 0.952

Asia WGS AF: 0.984 AC: 3421 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	MEGF10-related myopathy (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	5.5
DANN	Benign	0.86
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs31483; hg19: chr5-126746277; COSMIC: COSV108037270;