Variant X-13600001-C-T 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.307C>T(p.Arg103Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000346 in 1,208,487 control chromosomes in the GnomAD database, including 3 homozygotes. There are 114 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., 62 hem., cov: 22)

Exomes 𝑓: 0.00019 ( 2 hom. 52 hem. )

Consequence

EGFL6
NM_015507.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.02

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=0.012380391).

BP6

Variant X-13600001-C-T is Benign according to our data. Variant chrX-13600001-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 711786.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAd4 at 62 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFL6	NM_015507.4 linkuse as main transcript	c.307C>T	p.Arg103Trp	missense_variant	4/12	ENST00000361306.6	NP_056322.2
EGFL6	NM_001167890.2 linkuse as main transcript	c.307C>T	p.Arg103Trp	missense_variant	4/12		NP_001161362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFL6	ENST00000361306.6 linkuse as main transcript	c.307C>T	p.Arg103Trp	missense_variant	4/12	1	NM_015507.4	ENSP00000355126	A2	Q8IUX8-1
EGFL6	ENST00000380602.3 linkuse as main transcript	c.307C>T	p.Arg103Trp	missense_variant	4/12	1		ENSP00000369976	P4	Q8IUX8-2

Frequencies

GnomAD3 genomes

AF:

0.00190

AC:

212

AN:

111620

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

AN XY:

33786

show subpopulations

Gnomad AFR

AF:

0.00656

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000573

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:

0.00333

GnomAD3 exomes

AF:

0.000547

AC:

100

AN:

182840

Hom.:

AF XY:

0.000253

AC XY:

AN XY:

67318

show subpopulations

Gnomad AFR exome

AF:

0.00672

Gnomad AMR exome

AF:

0.000403

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:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000188

AC:

206

AN:

1096814

Hom.:

Cov.:

AF XY:

0.000144

AC XY:

AN XY:

362196

show subpopulations

Gnomad4 AFR exome

AF:

0.00668

Gnomad4 AMR exome

AF:

0.000398

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000185

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.00190

AC:

212

AN:

111673

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

AN XY:

33849

show subpopulations

Gnomad4 AFR

AF:

0.00654

Gnomad4 AMR

AF:

0.000573

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:

0.00329

Alfa

AF:

0.000271

Hom.:

Bravo

AF:

0.00210

ESP6500AA

AF:

0.00600

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000667

AC:

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	Nov 24, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.51

D;.

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D

M_CAP

Pathogenic

0.43

MetaRNN

Benign

0.012

T;T

MetaSVM

Uncertain

0.63

MutationAssessor

Benign

1.5

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-7.6

D;D

REVEL

Uncertain

0.60

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;P

Vest4

0.43

MVP

0.53

MPC

0.89

ClinPred

0.18

GERP RS

4.2

Varity_R

0.83

gMVP

0.74

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