Variant X-13594871-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015507.4(EGFL6):c.223G>A(p.Val75Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00657 in 1,209,135 control chromosomes in the GnomAD database, including 31 homozygotes. There are 2,527 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 4 hom., 193 hem., cov: 23)

Exomes 𝑓: 0.0067 ( 27 hom. 2334 hem. )

Consequence

EGFL6
NM_015507.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.10

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 Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008598298).

BP6

Variant X-13594871-G-A is Benign according to our data. Variant chrX-13594871-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 789545.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFL6	NM_015507.4 linkuse as main transcript	c.223G>A	p.Val75Met	missense_variant	3/12	ENST00000361306.6
EGFL6	NM_001167890.2 linkuse as main transcript	c.223G>A	p.Val75Met	missense_variant	3/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFL6	ENST00000361306.6 linkuse as main transcript	c.223G>A	p.Val75Met	missense_variant	3/12	1	NM_015507.4	A2	Q8IUX8-1
EGFL6	ENST00000380602.3 linkuse as main transcript	c.223G>A	p.Val75Met	missense_variant	3/12	1		P4	Q8IUX8-2

Frequencies

GnomAD3 genomes

AF:

0.00552

AC:

617

AN:

111786

Hom.:

Cov.:

AF XY:

0.00568

AC XY:

193

AN XY:

33980

show subpopulations

Gnomad AFR

AF:

0.00121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00617

Gnomad ASJ

AF:

0.0121

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000746

Gnomad FIN

AF:

0.00777

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00797

Gnomad OTH

AF:

0.00674

GnomAD3 exomes

AF:

0.00427

AC:

781

AN:

183011

Hom.:

AF XY:

0.00403

AC XY:

272

AN XY:

67517

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00816

Gnomad EAS exome

AF:

0.0000723

Gnomad SAS exome

AF:

0.000631

Gnomad FIN exome

AF:

0.00656

Gnomad NFE exome

AF:

0.00656

Gnomad OTH exome

AF:

0.00443

GnomAD4 exome

AF:

0.00667

AC:

7322

AN:

1097295

Hom.:

Cov.:

AF XY:

0.00643

AC XY:

2334

AN XY:

362723

show subpopulations

Gnomad4 AFR exome

AF:

0.000606

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00837

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.00109

Gnomad4 FIN exome

AF:

0.00755

Gnomad4 NFE exome

AF:

0.00766

Gnomad4 OTH exome

AF:

0.00569

GnomAD4 genome

AF:

0.00551

AC:

616

AN:

111840

Hom.:

Cov.:

AF XY:

0.00567

AC XY:

193

AN XY:

34044

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.00616

Gnomad4 ASJ

AF:

0.0121

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000748

Gnomad4 FIN

AF:

0.00777

Gnomad4 NFE

AF:

0.00795

Gnomad4 OTH

AF:

0.00665

Alfa

AF:

0.00695

Hom.:

116

Bravo

AF:

0.00529

TwinsUK

AF:

0.0102

AC:

ALSPAC

AF:

0.0104

AC:

ESP6500AA

AF:

0.00209

AC:

ESP6500EA

AF:

0.00788

AC:

ExAC

AF:

0.00471

AC:

572

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0088

T;.

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-0.34

MutationAssessor

Benign

1.4

L;L

MutationTaster

Benign

0.98

D;D

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.9

N;N

REVEL

Uncertain

0.32

Sift

Benign

0.086

T;T

Sift4G

Benign

0.070

T;T

Polyphen

0.71

P;D

Vest4

0.15

MVP

0.74

MPC

0.79

ClinPred

0.012

GERP RS

4.1

Varity_R

0.13

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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