Genetic Variant EGFL6:p.Thr131Thr (chrX-13600087-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_015507.4(EGFL6):c.393G>A(p.Thr131Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000579 in 1,208,708 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 0.0000090 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000055 ( 0 hom. 3 hem. )

Consequence

EGFL6
NM_015507.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.76

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant X-13600087-G-A is Benign according to our data. Variant chrX-13600087-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2660025.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.76 with no splicing effect.

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL6	NM_015507.4 link	c.393G>A	p.Thr131Thr	synonymous_variant	Exon 4 of 12	ENST00000361306.6	NP_056322.2	Q8IUX8-1
EGFL6	NM_001167890.2 link	c.393G>A	p.Thr131Thr	synonymous_variant	Exon 4 of 12		NP_001161362.1	Q8IUX8-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFL6	ENST00000361306.6 link	c.393G>A	p.Thr131Thr	synonymous_variant	Exon 4 of 12	1	NM_015507.4	ENSP00000355126.1		Q8IUX8-1
EGFL6	ENST00000380602.3 link	c.393G>A	p.Thr131Thr	synonymous_variant	Exon 4 of 12	1		ENSP00000369976.3		Q8IUX8-2

Frequencies

GnomAD3 genomes

AF:

0.00000897

AC:

AN:

111521

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33697

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000168

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000276

AC:

AN:

181418

Hom.:

AF XY:

0.0000303

AC XY:

AN XY:

65920

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000533

Gnomad FIN exome

AF:

0.0000633

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1097137

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

362531

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000285

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:

0.0000434

GnomAD4 genome

AF:

0.00000896

AC:

AN:

111571

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33757

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000168

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000599

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

EGFL6: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.17

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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