chr5-127299745-GT-G

Position:

• chr5-127299745-GT-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000503335.7(MEGF10):​c.-19+8702del 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 ENST00000503335.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.355

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 Benign. Variant got -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/exons	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.-19+8702del		intron_variant		ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.-19+8702del		intron_variant		1	NM_001256545.2	ENSP00000423354	P1
MEGF10	ENST00000274473.6	c.-69-238del		intron_variant		1		ENSP00000274473	P1
MEGF10	ENST00000418761.6	c.-69-238del		intron_variant		1		ENSP00000416284
MEGF10	ENST00000508365.5	c.-19+8702del		intron_variant		1		ENSP00000423195

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

Gnomad4 AFR AF: 0.602

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.565

Gnomad4 EAS AF: 0.316

Gnomad4 SAS AF: 0.498

Gnomad4 FIN AF: 0.592

Gnomad4 NFE AF: 0.651

Gnomad4 OTH AF: 0.592

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 29, 2020

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs35796097; hg19: chr5-126635437;