Variant X-13603403-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_015507.4(EGFL6):c.487C>T(p.Leu163Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000868 in 1,209,185 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 32 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000090 ( 0 hom. 31 hem. )

Consequence

EGFL6
NM_015507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.73

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 -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.816

BS2

High Hemizygotes in GnomAdExome4 at 31 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFL6	NM_015507.4 linkuse as main transcript	c.487C>T	p.Leu163Phe	missense_variant	5/12	ENST00000361306.6	NP_056322.2
EGFL6	NM_001167890.2 linkuse as main transcript	c.487C>T	p.Leu163Phe	missense_variant	5/12		NP_001161362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFL6	ENST00000361306.6 linkuse as main transcript	c.487C>T	p.Leu163Phe	missense_variant	5/12	1	NM_015507.4	ENSP00000355126	A2	Q8IUX8-1
EGFL6	ENST00000380602.3 linkuse as main transcript	c.487C>T	p.Leu163Phe	missense_variant	5/12	1		ENSP00000369976	P4	Q8IUX8-2

Frequencies

GnomAD3 genomes

AF:

0.0000534

AC:

AN:

112433

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34571

show subpopulations

Gnomad AFR

AF:

0.0000323

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000938

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000499

AC:

AN:

180397

Hom.:

AF XY:

0.0000616

AC XY:

AN XY:

64933

show subpopulations

Gnomad AFR exome

AF:

0.0000768

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:

0.0000865

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.0000903

AC:

AN:

1096752

Hom.:

Cov.:

AF XY:

0.0000856

AC XY:

AN XY:

362164

show subpopulations

Gnomad4 AFR exome

AF:

0.0000380

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:

0.000112

Gnomad4 OTH exome

AF:

0.0000869

GnomAD4 genome

AF:

0.0000534

AC:

AN:

112433

Hom.:

Cov.:

AF XY:

0.0000289

AC XY:

AN XY:

34571

show subpopulations

Gnomad4 AFR

AF:

0.0000323

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000938

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000214

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000824

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

Nov 22, 2022

The c.487C>T (p.L163F) alteration is located in exon 5 (coding exon 5) of the EGFL6 gene. This alteration results from a C to T substitution at nucleotide position 487, causing the leucine (L) at amino acid position 163 to be replaced by a phenylalanine (F). 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

0.29

BayesDel_addAF

Uncertain

0.022

BayesDel_noAF

Uncertain

0.0

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

T;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.066

MetaRNN

Pathogenic

0.82

D;D

MetaSVM

Uncertain

0.41

MutationAssessor

Benign

0.59

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.9

D;D

REVEL

Uncertain

0.49

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.047

D;D

Polyphen

1.0

D;D

Vest4

0.71

MVP

0.36

MPC

0.91

ClinPred

0.45

GERP RS

5.1

Varity_R

0.85

gMVP

0.78

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