chr9-136670247-G-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016215.5(EGFL7):​c.488G>T​(p.Cys163Phe) variant causes a missense change. 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: 34)

Consequence

EGFL7
NM_016215.5 missense

Scores

12
6
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88
Variant links:
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]

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ACMG classification

Classification made for transcript

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, 0.991

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
EGFL7NM_016215.5 linkc.488G>T p.Cys163Phe missense_variant 8/11 ENST00000308874.12 NP_057299.1 Q9UHF1A0A024R8F5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
EGFL7ENST00000308874.12 linkc.488G>T p.Cys163Phe missense_variant 8/111 NM_016215.5 ENSP00000307843.7 Q9UHF1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
34

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 08, 2024The c.488G>T (p.C163F) alteration is located in exon 8 (coding exon 5) of the EGFL7 gene. This alteration results from a G to T substitution at nucleotide position 488, causing the cysteine (C) at amino acid position 163 to be replaced by a phenylalanine (F). 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
0.57
BayesDel_addAF
Pathogenic
0.40
D
BayesDel_noAF
Pathogenic
0.33
CADD
Uncertain
26
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.94
D;D;D;D
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.49
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
.;D;.;.
M_CAP
Pathogenic
0.60
D
MetaRNN
Pathogenic
0.99
D;D;D;D
MetaSVM
Pathogenic
1.0
D
MutationAssessor
Pathogenic
5.1
H;H;H;H
PrimateAI
Uncertain
0.65
T
PROVEAN
Pathogenic
-9.6
D;D;D;D
REVEL
Pathogenic
0.83
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
D;D;D;D
Vest4
0.74
MutPred
0.94
Loss of catalytic residue at W164 (P = 0.0214);Loss of catalytic residue at W164 (P = 0.0214);Loss of catalytic residue at W164 (P = 0.0214);Loss of catalytic residue at W164 (P = 0.0214);
MVP
1.0
MPC
0.60
ClinPred
1.0
D
GERP RS
4.3
Varity_R
0.99
gMVP
0.96

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr9-139564699; API