Variant 15-65898081-A-T 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.3276T>A(p.Ser1092Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,250 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MEGF11
NM_001385028.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.07

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.3276T>A	p.Ser1092Arg	missense_variant	26/26	ENST00000395614.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF11	ENST00000395614.6 linkuse as main transcript	c.3276T>A	p.Ser1092Arg	missense_variant	26/26	5	NM_001385028.1	A1
MEGF11	ENST00000422354.6 linkuse as main transcript	c.2988T>A	p.Ser996Arg	missense_variant	23/23	1		P2	A6BM72-1
MEGF11	ENST00000288745.7 linkuse as main transcript	c.2763T>A	p.Ser921Arg	missense_variant	21/21	1			A6BM72-2
MEGF11	ENST00000409699.6 linkuse as main transcript	c.2988T>A	p.Ser996Arg	missense_variant	23/23	5		P2	A6BM72-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249908

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1461250

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

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

Jun 04, 2024

The c.2988T>A (p.S996R) alteration is located in exon 23 (coding exon 22) of the MEGF11 gene. This alteration results from a T to A substitution at nucleotide position 2988, causing the serine (S) at amino acid position 996 to be replaced by an arginine (R). 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

0.68

BayesDel_addAF

Uncertain

0.099

BayesDel_noAF

Pathogenic

0.17

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.040

T;.;T;.

Eigen

Benign

0.14

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.95

.;D;D;D

M_CAP

Uncertain

0.13

MetaRNN

Uncertain

0.62

D;D;D;D

MetaSVM

Uncertain

0.12

MutationAssessor

Uncertain

2.7

M;.;M;.

MutationTaster

Benign

0.87

D;D;D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.3

N;N;N;.

REVEL

Uncertain

0.61

Sift

Benign

0.20

T;T;T;.

Sift4G

Benign

0.29

T;T;T;T

Polyphen

0.93

P;D;P;.

Vest4

0.62

MutPred

0.37

Loss of catalytic residue at S996 (P = 0.0591);.;Loss of catalytic residue at S996 (P = 0.0591);.;

MVP

0.67

MPC

0.13

ClinPred

0.55

GERP RS

3.9

Varity_R

0.17

gMVP

0.31

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