dbSNP rs1279159853: ANGPTL4:p.Thr62Asn (chr19-8364506-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_139314.3(ANGPTL4):c.185C>A(p.Thr62Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000708 in 1,412,096 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T62I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ANGPTL4
NM_139314.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.02

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.185C>A	p.Thr62Asn	missense	Exon 1 of 7	NP_647475.1	Q9BY76-1
ANGPTL4	NM_001039667.3		c.185C>A	p.Thr62Asn	missense	Exon 1 of 6	NP_001034756.1	Q9BY76-2
ANGPTL4	NR_104213.2		n.352C>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ANGPTL4	ENST00000301455.7	TSL:1 MANE Select	c.185C>A	p.Thr62Asn	missense	Exon 1 of 7	ENSP00000301455.1	Q9BY76-1
ANGPTL4	ENST00000593998.5	TSL:1	n.185C>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000472551.1	Q9BY76-1
ANGPTL4	ENST00000955923.1		c.185C>A	p.Thr62Asn	missense	Exon 2 of 8	ENSP00000625982.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.08e-7

AC:

AN:

1412096

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

698030

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32466

American (AMR)

AF:

0.00

AC:

AN:

37272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25214

East Asian (EAS)

AF:

0.00

AC:

AN:

37132

South Asian (SAS)

AF:

0.00

AC:

AN:

80430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48430

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5054

European-Non Finnish (NFE)

AF:

9.19e-7

AC:

AN:

1087662

Other (OTH)

AF:

0.00

AC:

AN:

58436

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

0.0075

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.78

M_CAP

Pathogenic

0.59

MetaRNN

Uncertain

0.65

MetaSVM

Benign

-0.54

MutationAssessor

Pathogenic

3.1

PhyloP100

5.0

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.30

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.62

MutPred

0.43

Loss of phosphorylation at T62 (P = 0.0407)

MVP

0.91

MPC

0.70

ClinPred

0.98

GERP RS

5.0

PromoterAI

0.10

Neutral

(source)

Varity_R

0.45

gMVP

0.89

Mutation Taster

=228/72

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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