X-13594910-G-C

Variant names:

• chrX-13594910-G-C
• NM_015507.4:c.262G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015507.4(EGFL6):​c.262G>C​(p.Gly88Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 23)
• Consequence: EGFL6 NM_015507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.68

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL6	NM_015507.4	c.262G>C	p.Gly88Arg	missense_variant	Exon 3 of 12	ENST00000361306.6	NP_056322.2
EGFL6	NM_001167890.2	c.262G>C	p.Gly88Arg	missense_variant	Exon 3 of 12		NP_001161362.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFL6	ENST00000361306.6	c.262G>C	p.Gly88Arg	missense_variant	Exon 3 of 12	1	NM_015507.4	ENSP00000355126.1
EGFL6	ENST00000380602.3	c.262G>C	p.Gly88Arg	missense_variant	Exon 3 of 12	1		ENSP00000369976.3

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.50	D
BayesDel_noAF	Pathogenic	0.48
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.17	T;.
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Pathogenic	0.53	D
MetaRNN	Uncertain	0.65	D;D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-7.3	D;D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		1.0	D;D
Vest4		0.32
MutPred		0.57		Loss of ubiquitination at K89 (P = 0.0334);Loss of ubiquitination at K89 (P = 0.0334);
MVP		0.73
MPC		0.96
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.88
gMVP		0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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-13613029;