rs121918382

Variant summary

Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5

The NM_000040.3(APOC3):c.232A>G(p.Lys78Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

APOC3
NM_000040.3 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 0.719

Variant links:

Genes affected

APOC3 (HGNC:610): (apolipoprotein C3) This gene encodes a protein component of triglyceride (TG)-rich lipoproteins (TRLs) including very low density lipoproteins (VLDL), high density lipoproteins (HDL) and chylomicrons. The encoded protein plays a role in role in the metabolism of these TRLs through multiple modes. This protein has been shown to promote the secretion of VLDL1, inhibit lipoprotein lipase enzyme activity, and delay catabolism of TRL remnants. Mutations in this gene are associated with low plasma triglyceride levels and reduced risk of ischemic cardiovascular disease, and hyperalphalipoproteinemia, which is characterized by elevated levels of high density lipoprotein (HDL) and HDL cholesterol in human patients. This gene and other related genes comprise an apolipoprotein gene cluster on chromosome 11. [provided by RefSeq, Sep 2017]

APOC3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 9 ACMG points.

PM1

In a region_of_interest Lipid-binding (size 31) in uniprot entity APOC3_HUMAN there are 5 pathogenic changes around while only 1 benign (83%) in NM_000040.3

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.969

PP5

Variant 11-116832816-A-G is Pathogenic according to our data. Variant chr11-116832816-A-G is described in ClinVar as [Pathogenic]. Clinvar id is 17903.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-116832816-A-G is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOC3	NM_000040.3 linkuse as main transcript	c.232A>G	p.Lys78Glu	missense_variant	4/4	ENST00000227667.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
APOC3	ENST00000227667.8 linkuse as main transcript	c.232A>G	p.Lys78Glu	missense_variant	4/4	1	NM_000040.3	P1
APOC3	ENST00000630701.1 linkuse as main transcript	c.286A>G	p.Lys96Glu	missense_variant	3/3	1
APOC3	ENST00000375345.3 linkuse as main transcript	c.286A>G	p.Lys96Glu	missense_variant	4/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251436

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Apolipoprotein c-III deficiency

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 1991

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.040

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Uncertain

0.69

D;.;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.63

T;.;T

M_CAP

Uncertain

0.13

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Benign

-0.58

MutationTaster

Benign

1.0e-11

A;A

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.1

N;N;.

REVEL

Uncertain

0.58

Sift

Benign

0.065

T;D;.

Sift4G

Benign

0.39

T;T;T

Polyphen

0.61

P;.;.

Vest4

0.69

MVP

0.91

MPC

0.47

ClinPred

0.94

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.16

gMVP

0.53

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

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