X-13589624-C-T

Position:

• chrX-13589624-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015507.4(EGFL6):​c.143C>T​(p.Ala48Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000173 in 1,097,293 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 0.000017 (0 hom. 10 hem.)
• Consequence: EGFL6 NM_015507.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18

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]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFL6	NM_015507.4	c.143C>T	p.Ala48Val	missense_variant	2/12	ENST00000361306.6	NP_056322.2
EGFL6	NM_001167890.2	c.143C>T	p.Ala48Val	missense_variant	2/12		NP_001161362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFL6	ENST00000361306.6	c.143C>T	p.Ala48Val	missense_variant	2/12	1	NM_015507.4	ENSP00000355126	A2
EGFL6	ENST00000380602.3	c.143C>T	p.Ala48Val	missense_variant	2/12	1		ENSP00000369976	P4

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.0000173 AC: 19 AN: 1097293 Hom.: 0 Cov.: 29 AF XY: 0.0000276 AC XY: 10 AN XY: 362743

Gnomad4 AFR exome AF: 0.00

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: 0.0000214

Gnomad4 OTH exome AF: 0.0000217

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 16, 2023

The c.143C>T (p.A48V) alteration is located in exon 2 (coding exon 2) of the EGFL6 gene. This alteration results from a C to T substitution at nucleotide position 143, causing the alanine (A) at amino acid position 48 to be replaced by a valine (V). 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	0.17
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0082	T;.
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.45	T;T
MetaSVM	Benign	-0.70	T
MutationAssessor	Benign	0.97	L;L
MutationTaster	Benign	0.70	D;D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.096
Sift	Uncertain	0.0080	D;D
Sift4G	Uncertain	0.026	D;D
Polyphen		0.79	P;P
Vest4		0.31
MutPred		0.41		Gain of methylation at K46 (P = 0.0643);Gain of methylation at K46 (P = 0.0643);
MVP		0.70
MPC		0.59
ClinPred		0.88	D
GERP RS		4.0
Varity_R		0.24
gMVP		0.27

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-13607743;