Variant 15-65898046-T-C 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.3311A>G(p.Tyr1104Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,236 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

MEGF11
NM_001385028.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37

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:

Genome browser will be placed here

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	Protein	UniProt
MEGF11	NM_001385028.1 link	c.3311A>G	p.Tyr1104Cys	missense_variant	26/26	ENST00000395614.6	NP_001371957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MEGF11	ENST00000395614.6 link	c.3311A>G	p.Tyr1104Cys	missense_variant	26/26	5	NM_001385028.1	ENSP00000378976.2	A0A0A0MS64
MEGF11	ENST00000422354.6 link	c.3023A>G	p.Tyr1008Cys	missense_variant	23/23	1		ENSP00000414475.1	A6BM72-1
MEGF11	ENST00000288745.7 link	c.2798A>G	p.Tyr933Cys	missense_variant	21/21	1		ENSP00000288745.3	A6BM72-2
MEGF11	ENST00000409699.6 link	c.3023A>G	p.Tyr1008Cys	missense_variant	23/23	5		ENSP00000386908.2	A6BM72-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Aug 19, 2024

The c.3023A>G (p.Y1008C) alteration is located in exon 23 (coding exon 22) of the MEGF11 gene. This alteration results from a A to G substitution at nucleotide position 3023, causing the tyrosine (Y) at amino acid position 1008 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Pathogenic

0.27

BayesDel_noAF

Pathogenic

0.14

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T;.

Eigen

Benign

0.18

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.76

.;T;T;T

M_CAP

Uncertain

0.14

MetaRNN

Uncertain

0.54

D;D;D;D

MetaSVM

Uncertain

-0.011

MutationAssessor

Uncertain

2.1

M;.;M;.

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-3.0

D;D;D;.

REVEL

Uncertain

0.62

Sift

Benign

0.069

T;D;T;.

Sift4G

Benign

0.11

T;T;T;T

Polyphen

0.99

D;D;D;.

Vest4

0.57

MutPred

0.44

Loss of loop (P = 0.0128);.;Loss of loop (P = 0.0128);.;

MVP

0.62

MPC

0.27

ClinPred

0.91

GERP RS

1.1

Varity_R

0.33

gMVP

0.26

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over