Variant chr20-881184-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000381922.5(ANGPT4):c.938C>T(p.Thr313Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,590,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

ANGPT4
ENST00000381922.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

Variant links:

Genes affected

ANGPT4 (HGNC:487): (angiopoietin 4) Angiopoietins are proteins with important roles in vascular development and angiogenesis. All angiopoietins bind with similar affinity to an endothelial cell-specific tyrosine-protein kinase receptor. The mechanism by which they contribute to angiogenesis is thought to involve regulation of endothelial cell interactions with supporting perivascular cells. The protein encoded by this gene functions as an agonist and is an angiopoietin. [provided by RefSeq, Jul 2008]

ANGPT4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11203566).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ANGPT4	NM_015985.4 linkuse as main transcript	c.938C>T	p.Thr313Met	missense_variant	5/9	ENST00000381922.5	NP_057069.1
ANGPT4	NM_001322809.2 linkuse as main transcript	c.938C>T	p.Thr313Met	missense_variant	5/8		NP_001309738.1
ANGPT4	XM_011529239.4 linkuse as main transcript	c.782C>T	p.Thr261Met	missense_variant	4/8		XP_011527541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ANGPT4	ENST00000381922.5 linkuse as main transcript	c.938C>T	p.Thr313Met	missense_variant	5/9	1	NM_015985.4	ENSP00000371347	P1	Q9Y264-1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000215

AC:

AN:

232834

Hom.:

AF XY:

0.0000239

AC XY:

AN XY:

125498

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000486

Gnomad NFE exome

AF:

0.00000945

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000153

AC:

AN:

1438720

Hom.:

Cov.:

AF XY:

0.0000224

AC XY:

AN XY:

713710

show subpopulations

Gnomad4 AFR exome

AF:

0.0000611

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000255

Gnomad4 SAS exome

AF:

0.0000483

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.0000118

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

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 submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.938C>T (p.T313M) alteration is located in exon 5 (coding exon 5) of the ANGPT4 gene. This alteration results from a C to T substitution at nucleotide position 938, causing the threonine (T) at amino acid position 313 to be replaced by a methionine (M). 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

Benign

0.10

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.083

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.40

M_CAP

Benign

0.0075

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.7

REVEL

Benign

0.026

Sift

Benign

0.058

Sift4G

Benign

0.15

Polyphen

0.42

Vest4

0.22

MVP

0.55

MPC

0.23

ClinPred

0.072

GERP RS

1.7

Varity_R

0.047

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over