Variant 22-36142005-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000424878.4(APOL3):c.191C>T(p.Ala64Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,614,086 control chromosomes in the GnomAD database, including 191 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 112 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 79 hom. )

Consequence

APOL3
ENST00000424878.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.22

Variant links:

Genes affected

APOL3 (HGNC:14868): (apolipoprotein L3) This gene is a member of the apolipoprotein L gene family, and it is present in a cluster with other family members on chromosome 22. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids, including cholesterol, and/or allow the binding of lipids to organelles. In addition, expression of this gene is up-regulated by tumor necrosis factor-alpha in endothelial cells lining the normal and atherosclerotic iliac artery and aorta. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2015]

APOL3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0025641024).

BP6

Variant 22-36142005-G-A is Benign according to our data. Variant chr22-36142005-G-A is described in ClinVar as [Benign]. Clinvar id is 789682.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0709 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL3	NM_145639.2 linkuse as main transcript	c.191C>T	p.Ala64Val	missense_variant	4/4	ENST00000424878.4	NP_663614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000424878.4 linkuse as main transcript	c.191C>T	p.Ala64Val	missense_variant	4/4	1	NM_145639.2	ENSP00000415779	A2	O95236-2

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3250

AN:

152110

Hom.:

111

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00975

Gnomad ASJ

AF:

0.00375

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.000676

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00599

AC:

1504

AN:

251084

Hom.:

AF XY:

0.00470

AC XY:

638

AN XY:

135716

show subpopulations

Gnomad AFR exome

AF:

0.0719

Gnomad AMR exome

AF:

0.00428

Gnomad ASJ exome

AF:

0.00636

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000679

Gnomad OTH exome

AF:

0.00539

GnomAD4 exome

AF:

0.00251

AC:

3674

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

1643

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0710

Gnomad4 AMR exome

AF:

0.00454

Gnomad4 ASJ exome

AF:

0.00566

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000429

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000452

Gnomad4 OTH exome

AF:

0.00604

GnomAD4 genome

AF:

0.0215

AC:

3276

AN:

152228

Hom.:

112

Cov.:

AF XY:

0.0211

AC XY:

1567

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0731

Gnomad4 AMR

AF:

0.00974

Gnomad4 ASJ

AF:

0.00375

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000676

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00519

Hom.:

Bravo

AF:

0.0245

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0690

AC:

304

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00713

AC:

866

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.0020

DANN

Benign

0.86

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.013

LIST_S2

Benign

0.41

T;T

MetaRNN

Benign

0.0026

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.1

L;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.60

N;.

REVEL

Benign

0.0080

Sift

Benign

0.57

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.14

B;B

Vest4

0.055

MVP

0.055

MPC

0.18

ClinPred

0.0040

GERP RS

-8.3

Varity_R

0.017

gMVP

0.057

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