X-13594871-G-T

Variant names:

• chrX-13594871-G-T
• rs141324039
• NM_015507.4:c.223G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015507.4(EGFL6):​c.223G>T​(p.Val75Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V75M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 23)
• Consequence: EGFL6 NM_015507.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10
• Publications: 4 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21209249).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015507.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL6	NM_015507.4	MANE Select	c.223G>T	p.Val75Leu	missense	Exon 3 of 12	NP_056322.2
	EGFL6	NM_001167890.2		c.223G>T	p.Val75Leu	missense	Exon 3 of 12	NP_001161362.1	Q8IUX8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL6	ENST00000361306.6	TSL:1 MANE Select	c.223G>T	p.Val75Leu	missense	Exon 3 of 12	ENSP00000355126.1	Q8IUX8-1
	EGFL6	ENST00000380602.3	TSL:1	c.223G>T	p.Val75Leu	missense	Exon 3 of 12	ENSP00000369976.3	Q8IUX8-2
	EGFL6	ENST00000857787.1		c.223G>T	p.Val75Leu	missense	Exon 3 of 11	ENSP00000527846.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 125

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0074	T
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.3	L
PhyloP100		3.1
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.9	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.018	D
Polyphen		0.28	B
Vest4		0.32
MutPred		0.30		Loss of ubiquitination at K70 (P = 0.0738)
MVP		0.74
MPC		0.47
ClinPred		0.86	D
GERP RS		4.1
Varity_R		0.24
gMVP		0.37
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs141324039; hg19: chrX-13612990;