Variant 15-65913940-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001385028.1(MEGF11):c.2507C>T(p.Thr836Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MEGF11
NM_001385028.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.37

Variant links:

Genes affected

MEGF11 (HGNC:29635): (multiple EGF like domains 11) Predicted to be involved in homotypic cell-cell adhesion and retina layer formation. Predicted to be located in basolateral plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

MEGF11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF11	NM_001385028.1 linkuse as main transcript	c.2507C>T	p.Thr836Ile	missense_variant	20/26	ENST00000395614.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF11	ENST00000395614.6 linkuse as main transcript	c.2507C>T	p.Thr836Ile	missense_variant	20/26	5	NM_001385028.1	A1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000799

AC:

AN:

250342

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135352

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461642

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.2507C>T (p.T836I) alteration is located in exon 20 (coding exon 19) of the MEGF11 gene. This alteration results from a C to T substitution at nucleotide position 2507, causing the threonine (T) at amino acid position 836 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T;.

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

.;D;D;D

M_CAP

Uncertain

0.19

MetaRNN

Uncertain

0.73

D;D;D;D

MetaSVM

Uncertain

0.46

MutationAssessor

Uncertain

2.6

M;.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.5

D;D;D;.

REVEL

Uncertain

0.62

Sift

Uncertain

0.0050

D;D;D;.

Sift4G

Uncertain

0.0060

D;D;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.85

MutPred

0.30

Loss of phosphorylation at T836 (P = 0.0484);.;Loss of phosphorylation at T836 (P = 0.0484);Loss of phosphorylation at T836 (P = 0.0484);

MVP

0.72

MPC

0.38

ClinPred

0.91

GERP RS

4.7

Varity_R

0.24

gMVP

0.75

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