NM_016215.5:c.420A>T

Variant names:

• chr9-136670179-A-T
• NM_016215.5:c.420A>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016215.5(EGFL7):​c.420A>T​(p.Glu140Asp) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: EGFL7 NM_016215.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.805
• Publications: 0 publications found

Genes affected

EGFL7 (HGNC:20594): (EGF like domain multiple 7) This gene encodes a secreted endothelial cell protein that contains two epidermal growth factor-like domains. The encoded protein may play a role in regulating vasculogenesis. This protein may be involved in the growth and proliferation of tumor cells. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.976

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016215.5. 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
	EGFL7	NM_016215.5	MANE Select	c.420A>T	p.Glu140Asp	missense	Exon 8 of 11	NP_057299.1	Q9UHF1
	EGFL7	NM_201446.3		c.420A>T	p.Glu140Asp	missense	Exon 6 of 9	NP_958854.1	Q9UHF1
	EGFL7	NR_045110.2		n.746A>T		non_coding_transcript_exon	Exon 7 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL7	ENST00000308874.12	TSL:1 MANE Select	c.420A>T	p.Glu140Asp	missense	Exon 8 of 11	ENSP00000307843.7	Q9UHF1
	EGFL7	ENST00000371698.3	TSL:1	c.420A>T	p.Glu140Asp	missense	Exon 6 of 9	ENSP00000360763.3	Q9UHF1
	EGFL7	ENST00000406555.7	TSL:1	c.420A>T	p.Glu140Asp	missense	Exon 7 of 10	ENSP00000385639.3	Q9UHF1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Pathogenic	0.35	D
BayesDel_noAF	Pathogenic	0.26
CADD	Benign	15
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.41	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.1	H
PhyloP100		-0.81
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.78
MutPred		0.84		Gain of phosphorylation at S142 (P = 0.279)
MVP		1.0
MPC		0.51
ClinPred		1.0	D
GERP RS		-3.4
Varity_R		0.93
gMVP		0.65
Mutation Taster		=62/38	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

hg19: chr9-139564631;