Genetic Variant ANGPTL4:p.Glu403Asp (chr19-8373874-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_139314.3(ANGPTL4):c.1209G>T(p.Glu403Asp) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

ANGPTL4
NM_139314.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.08

Publications

0 publications found

Variant links:

Genes affected

ANGPTL4 (HGNC:16039): (angiopoietin like 4) This gene encodes a glycosylated, secreted protein containing a C-terminal fibrinogen domain. The encoded protein is induced by peroxisome proliferation activators and functions as a serum hormone that regulates glucose homeostasis, lipid metabolism, and insulin sensitivity. This protein can also act as an apoptosis survival factor for vascular endothelial cells and can prevent metastasis by inhibiting vascular growth and tumor cell invasion. The C-terminal domain may be proteolytically-cleaved from the full-length secreted protein. Decreased expression of this gene has been associated with type 2 diabetes. Alternative splicing results in multiple transcript variants. This gene was previously referred to as ANGPTL2 but has been renamed ANGPTL4. [provided by RefSeq, Sep 2013]

ANGPTL4 links:

RAB11B-AS1 (HGNC:44178): (RAB11B antisense RNA 1)

RAB11B-AS1 links:

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ACMG classification

Classification was made for transcript

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=0.072817475).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139314.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANGPTL4	NM_139314.3	MANE Select	c.1209G>T	p.Glu403Asp	missense	Exon 7 of 7	NP_647475.1	Q9BY76-1
ANGPTL4	NM_001039667.3		c.1095G>T	p.Glu365Asp	missense	Exon 6 of 6	NP_001034756.1	Q9BY76-2
ANGPTL4	NR_104213.2		n.597-319G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANGPTL4	ENST00000301455.7	TSL:1 MANE Select	c.1209G>T	p.Glu403Asp	missense	Exon 7 of 7	ENSP00000301455.1	Q9BY76-1
ANGPTL4	ENST00000593998.5	TSL:1	n.1209G>T		non_coding_transcript_exon	Exon 7 of 8	ENSP00000472551.1	Q9BY76-1
ANGPTL4	ENST00000955923.1		c.1209G>T	p.Glu403Asp	missense	Exon 8 of 8	ENSP00000625982.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.0090

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.041

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.099

LIST_S2

Benign

0.34

M_CAP

Benign

0.012

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PhyloP100

-1.1

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.71

REVEL

Benign

0.018

Sift

Benign

0.15

Sift4G

Benign

0.098

Polyphen

0.0010

Vest4

0.064

MutPred

0.19

Loss of disorder (P = 0.2195)

MVP

0.41

MPC

0.17

ClinPred

0.10

GERP RS

-8.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

gMVP

0.43

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over