5-127299745-GT-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001256545.2(MEGF10):​c.-19+8702delT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.60 (26610 hom., cov: 0)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 5-127299745-GT-G is Benign according to our data. Variant chr5-127299745-GT-G is described in ClinVar as [Benign]. Clinvar id is 1233494.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.605 AC: 88246 AN: 145958 Hom.: 26596 Cov.: 0

Gnomad AFR AF: 0.602

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.542

Gnomad ASJ AF: 0.565

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.656

Gnomad NFE AF: 0.651

Gnomad OTH AF: 0.588

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

GnomAD4 genome AF: 0.605 AC: 88277 AN: 146006 Hom.: 26610 Cov.: 0 AF XY: 0.597 AC XY: 42325 AN XY: 70932

African (AFR) AF: 0.602 AC: 24028 AN: 39904

American (AMR) AF: 0.542 AC: 7926 AN: 14626

Ashkenazi Jewish (ASJ) AF: 0.565 AC: 1928 AN: 3414

East Asian (EAS) AF: 0.316 AC: 1578 AN: 4992

South Asian (SAS) AF: 0.498 AC: 2288 AN: 4598

European-Finnish (FIN) AF: 0.592 AC: 5346 AN: 9038

Middle Eastern (MID) AF: 0.652 AC: 184 AN: 282

European-Non Finnish (NFE) AF: 0.651 AC: 43095 AN: 66236

Other (OTH) AF: 0.592 AC: 1195 AN: 2020

Alfa AF: 0.417 Hom.: 773

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.35
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: rs35796097; hg19: chr5-126635437;