Variant 15-65897939-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001385028.1(MEGF11):c.3418T>C(p.Ser1140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000116 in 1,461,326 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MEGF11
NM_001385028.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.472

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:

Genome browser will be placed here

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;

BP4

Computational evidence support a benign effect (MetaRNN=0.0856092).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF11	NM_001385028.1 linkuse as main transcript	c.3418T>C	p.Ser1140Pro	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.3418T>C	p.Ser1140Pro	missense_variant	26/26	5	NM_001385028.1	A1
MEGF11	ENST00000422354.6 linkuse as main transcript	c.3130T>C	p.Ser1044Pro	missense_variant	23/23	1		P2	A6BM72-1
MEGF11	ENST00000288745.7 linkuse as main transcript	c.2905T>C	p.Ser969Pro	missense_variant	21/21	1			A6BM72-2
MEGF11	ENST00000409699.6 linkuse as main transcript	c.3130T>C	p.Ser1044Pro	missense_variant	23/23	5		P2	A6BM72-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250294

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135260

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461326

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

726970

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Dec 20, 2023

The c.3130T>C (p.S1044P) alteration is located in exon 23 (coding exon 22) of the MEGF11 gene. This alteration results from a T to C substitution at nucleotide position 3130, causing the serine (S) at amino acid position 1044 to be replaced by a proline (P). 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

Benign

0.075

BayesDel_addAF

Uncertain

0.089

BayesDel_noAF

Benign

-0.11

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.0077

T;.;T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.61

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.76

.;T;T;T

M_CAP

Benign

0.063

MetaRNN

Benign

0.086

T;T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

0.69

N;.;N;.

MutationTaster

Benign

1.0

D;N;N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Benign

0.63

N;N;N;.

REVEL

Uncertain

0.42

Sift

Uncertain

0.0090

D;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.19

B;B;B;.

Vest4

0.16

MutPred

0.089

Loss of phosphorylation at S1044 (P = 0.0149);.;Loss of phosphorylation at S1044 (P = 0.0149);.;

MVP

0.43

MPC

0.16

ClinPred

0.14

GERP RS

1.3

Varity_R

0.12

gMVP

0.14

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