chrX-13608342-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015507.4(EGFL6):c.674T>C(p.Met225Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 1,209,183 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000090 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Consequence

EGFL6
NM_015507.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.971

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057520747).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL6	NM_015507.4 link	c.674T>C	p.Met225Thr	missense_variant	Exon 7 of 12	ENST00000361306.6	NP_056322.2	Q8IUX8-1
EGFL6	NM_001167890.2 link	c.674T>C	p.Met225Thr	missense_variant	Exon 7 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.674T>C	p.Met225Thr	missense_variant	Exon 7 of 12	1	NM_015507.4	ENSP00000355126.1		Q8IUX8-1
EGFL6	ENST00000380602.3 link	c.674T>C	p.Met225Thr	missense_variant	Exon 7 of 12	1		ENSP00000369976.3		Q8IUX8-2

Frequencies

GnomAD3 genomes

AF:

0.0000895

AC:

AN:

111689

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000293

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000952

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:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183382

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000152

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.00000547

AC:

AN:

1097494

Hom.:

Cov.:

AF XY:

0.00000551

AC XY:

AN XY:

362872

show subpopulations

African (AFR)

AF:

0.000152

AC:

AN:

26380

American (AMR)

AF:

0.0000284

AC:

AN:

35197

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19369

East Asian (EAS)

AF:

0.00

AC:

AN:

30182

South Asian (SAS)

AF:

0.0000185

AC:

AN:

54078

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40495

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

841597

Other (OTH)

AF:

0.00

AC:

AN:

46064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000895

AC:

AN:

111689

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33867

show subpopulations

African (AFR)

AF:

0.000293

AC:

AN:

30695

American (AMR)

AF:

0.0000952

AC:

AN:

10508

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2642

East Asian (EAS)

AF:

0.00

AC:

AN:

3573

South Asian (SAS)

AF:

0.00

AC:

AN:

2617

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6041

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53179

Other (OTH)

AF:

0.00

AC:

AN:

1512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

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

Sep 25, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.674T>C (p.M225T) alteration is located in exon 7 (coding exon 7) of the EGFL6 gene. This alteration results from a T to C substitution at nucleotide position 674, causing the methionine (M) at amino acid position 225 to be replaced by a threonine (T). 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

0.064

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.56

CADD

Benign

0.040

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.097

T;.

FATHMM_MKL

Benign

0.042

LIST_S2

Uncertain

0.88

D;D

M_CAP

Benign

0.054

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

-0.46

N;N

PhyloP100

-0.97

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.18

Sift

Benign

0.18

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.0010

B;B

Vest4

0.13

MVP

0.32

MPC

0.28

ClinPred

0.022

GERP RS

-6.5

Varity_R

0.11

gMVP

0.75

Mutation Taster

=92/8

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over