Variant X-13594880-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_015507.4(EGFL6):c.232A>G(p.Asn78Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,209,334 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000012 ( 0 hom. 3 hem. )

Consequence

EGFL6
NM_015507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.08

Variant links:

Genes affected

EGFL6 (HGNC:3235): (EGF like domain multiple 6) This gene encodes a member of the epidermal growth factor (EGF) repeat superfamily. Members of this superfamily are characterized by the presence of EGF-like repeats and are often involved in the regulation of cell cycle, proliferation, and developmental processes. The gene product contains a signal peptide, suggesting that it is secreted; an EGF repeat region consisting of 4 complete EGF-like repeats and 1 partial EGF-like repeat, 3 of which have a calcium-binding consensus sequence; an arg-gly-asp integrin association motif; and a MAM domain, which is believed to have an adhesive function. This gene is expressed early during development, and its expression has been detected in lung and meningioma tumors. [provided by RefSeq, Jul 2008]

EGFL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3427224).

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFL6	NM_015507.4 linkuse as main transcript	c.232A>G	p.Asn78Asp	missense_variant	3/12	ENST00000361306.6
EGFL6	NM_001167890.2 linkuse as main transcript	c.232A>G	p.Asn78Asp	missense_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFL6	ENST00000361306.6 linkuse as main transcript	c.232A>G	p.Asn78Asp	missense_variant	3/12	1	NM_015507.4	A2	Q8IUX8-1
EGFL6	ENST00000380602.3 linkuse as main transcript	c.232A>G	p.Asn78Asp	missense_variant	3/12	1		P4	Q8IUX8-2

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111925

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34101

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000558

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

GnomAD3 exomes

AF:

0.00000546

AC:

AN:

183010

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000723

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:

0.0000118

AC:

AN:

1097409

Hom.:

Cov.:

AF XY:

0.00000827

AC XY:

AN XY:

362815

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000431

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111925

Hom.:

Cov.:

AF XY:

0.0000293

AC XY:

AN XY:

34101

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000558

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Dec 20, 2023

The c.232A>G (p.N78D) alteration is located in exon 3 (coding exon 3) of the EGFL6 gene. This alteration results from a A to G substitution at nucleotide position 232, causing the asparagine (N) at amino acid position 78 to be replaced by an aspartic acid (D). 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

0.17

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.034

T;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.34

T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

0.070

N;N

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Uncertain

0.37

Sift

Benign

0.065

T;T

Sift4G

Benign

0.10

T;T

Polyphen

0.86

P;P

Vest4

0.50

MutPred

0.46

Gain of ubiquitination at K79 (P = 0.0483);Gain of ubiquitination at K79 (P = 0.0483);

MVP

0.76

MPC

0.32

ClinPred

0.98

GERP RS

5.0

Varity_R

0.78

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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