5-127299745-GTT-GTTT

Variant names:

• chr5-127299745-G-GT
• rs35796097
• NM_001256545.2:c.-19+8702dupT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS1

The NM_001256545.2(MEGF10):​c.-19+8702dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0021 (1 hom., cov: 0)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.355
• Publications: 0 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00211 (309/146112) while in subpopulation AFR AF = 0.00526 (210/39928). AF 95% confidence interval is 0.00468. There are 1 homozygotes in GnomAd4. There are 157 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.-19+8702dupT		intron_variant	Intron 1 of 24	ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.-19+8689_-19+8690insT		intron_variant	Intron 1 of 24	1	NM_001256545.2	ENSP00000423354.2
MEGF10	ENST00000274473.6	c.-69-251_-69-250insT		intron_variant	Intron 1 of 25	1		ENSP00000274473.6
MEGF10	ENST00000418761.6	c.-69-251_-69-250insT		intron_variant	Intron 1 of 14	1		ENSP00000416284.2
MEGF10	ENST00000508365.5	c.-19+8689_-19+8690insT		intron_variant	Intron 1 of 13	1		ENSP00000423195.1

Frequencies

GnomAD3 genomes AF: 0.00211 AC: 308 AN: 146064 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00525

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00198

Gnomad ASJ AF: 0.00176

Gnomad EAS AF: 0.000998

Gnomad SAS AF: 0.00108

Gnomad FIN AF: 0.00210

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000437

Gnomad OTH AF: 0.00299

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.00211 AC: 309 AN: 146112 Hom.: 1 Cov.: 0 AF XY: 0.00221 AC XY: 157 AN XY: 70988

African (AFR) AF: 0.00526 AC: 210 AN: 39928

American (AMR) AF: 0.00198 AC: 29 AN: 14638

Ashkenazi Jewish (ASJ) AF: 0.00176 AC: 6 AN: 3418

East Asian (EAS) AF: 0.00100 AC: 5 AN: 4994

South Asian (SAS) AF: 0.00109 AC: 5 AN: 4606

European-Finnish (FIN) AF: 0.00210 AC: 19 AN: 9052

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 282

European-Non Finnish (NFE) AF: 0.000438 AC: 29 AN: 66278

Other (OTH) AF: 0.00297 AC: 6 AN: 2020

Alfa AF: 0.000650 Hom.: 773

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.35

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: rs35796097; hg19: chr5-126635437;