5-127299745-GTT-GTTTT

Variant names:

• chr5-127299745-G-GTT
• rs35796097
• NM_001256545.2:c.-19+8701_-19+8702dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001256545.2(MEGF10):​c.-19+8701_-19+8702dupTT 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 0.000034 (0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.-19+8701_-19+8702dupTT		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+8690insTT		intron_variant	Intron 1 of 24	1	NM_001256545.2	ENSP00000423354.2
MEGF10	ENST00000274473.6	c.-69-251_-69-250insTT		intron_variant	Intron 1 of 25	1		ENSP00000274473.6
MEGF10	ENST00000418761.6	c.-69-251_-69-250insTT		intron_variant	Intron 1 of 14	1		ENSP00000416284.2
MEGF10	ENST00000508365.5	c.-19+8689_-19+8690insTT		intron_variant	Intron 1 of 13	1		ENSP00000423195.1

Frequencies

GnomAD3 genomes AF: 0.0000342 AC: 5 AN: 146102 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000251

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000110

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000452

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000342 AC: 5 AN: 146102 Hom.: 0 Cov.: 0 AF XY: 0.0000141 AC XY: 1 AN XY: 70938

African (AFR) AF: 0.0000251 AC: 1 AN: 39846

American (AMR) AF: 0.00 AC: 0 AN: 14632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3418

East Asian (EAS) AF: 0.00 AC: 0 AN: 5008

South Asian (SAS) AF: 0.00 AC: 0 AN: 4622

European-Finnish (FIN) AF: 0.000110 AC: 1 AN: 9060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 308

European-Non Finnish (NFE) AF: 0.0000452 AC: 3 AN: 66304

Other (OTH) AF: 0.00 AC: 0 AN: 2008

Alfa AF: 0.00 Hom.: 773

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs35796097; hg19: chr5-126635437;