Variant chr5-127331273-A-AT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_001256545.2(MEGF10):c.-18-12dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,335,974 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

MEGF10
NM_001256545.2 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.481

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 5-127331273-A-AT is Benign according to our data. Variant chr5-127331273-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 1188266.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF10	NM_001256545.2 linkuse as main transcript	c.-18-12dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7 linkuse as main transcript	c.-18-12dup	splice_polypyrimidine_tract_variant, intron_variant	1	NM_001256545.2	ENSP00000423354	P1	Q96KG7-1
MEGF10	ENST00000274473.6 linkuse as main transcript	c.-18-12dup	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000274473	P1	Q96KG7-1
MEGF10	ENST00000418761.6 linkuse as main transcript	c.-18-12dup	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000416284		Q96KG7-2
MEGF10	ENST00000508365.5 linkuse as main transcript	c.-18-12dup	splice_polypyrimidine_tract_variant, intron_variant	1		ENSP00000423195		Q96KG7-2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151804

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000711

AC:

AN:

239262

Hom.:

AF XY:

0.0000464

AC XY:

AN XY:

129412

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000472

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000568

Gnomad SAS exome

AF:

0.0000354

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000194

AC:

AN:

1184052

Hom.:

Cov.:

AF XY:

0.0000183

AC XY:

AN XY:

602626

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000430

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000126

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151922

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74234

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 02, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over