chr9-136670179-A-T

Position:

• chr9-136670179-A-T

Variant summary

Our verdict is Likely pathogenic. Variant got 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

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EGFL7	NM_016215.5	c.420A>T	p.Glu140Asp	missense_variant	8/11	ENST00000308874.12	NP_057299.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFL7	ENST00000308874.12	c.420A>T	p.Glu140Asp	missense_variant	8/11	1	NM_016215.5	ENSP00000307843	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

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

Aug 15, 2023

The c.420A>T (p.E140D) alteration is located in exon 8 (coding exon 5) of the EGFL7 gene. This alteration results from a A to T substitution at nucleotide position 420, causing the glutamic acid (E) at amino acid position 140 to be replaced by an aspartic acid (D). 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	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;D;D;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;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.1	H;H;H;H
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.6	D;D;D;D
REVEL	Pathogenic	0.78
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Uncertain	0.012	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.78
MutPred		0.84		Gain of phosphorylation at S142 (P = 0.279);Gain of phosphorylation at S142 (P = 0.279);Gain of phosphorylation at S142 (P = 0.279);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-139564631;