chr22-36141280-G-A

Variant summary

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

The NM_145639.2(APOL3):​c.916C>T​(p.Arg306Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,614,100 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 0.000079 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

APOL3
NM_145639.2 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.520
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]

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=0.21820629).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
APOL3NM_145639.2 linkuse as main transcriptc.916C>T p.Arg306Trp missense_variant 4/4 ENST00000424878.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APOL3ENST00000424878.4 linkuse as main transcriptc.916C>T p.Arg306Trp missense_variant 4/41 NM_145639.2 A2O95236-2

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152088
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000725
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:
0.00316
Gnomad NFE
AF:
0.000118
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000795
AC:
20
AN:
251458
Hom.:
0
AF XY:
0.0000809
AC XY:
11
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000326
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.0000528
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000137
AC:
201
AN:
1461894
Hom.:
0
Cov.:
29
AF XY:
0.000132
AC XY:
96
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000327
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.000206
Gnomad4 NFE exome
AF:
0.000135
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.0000788
AC:
12
AN:
152206
Hom.:
0
Cov.:
31
AF XY:
0.0000403
AC XY:
3
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0000723
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:
0.000118
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000184
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000824
AC:
10
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

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 submitterclinical testingAmbry GeneticsDec 07, 2023The c.1129C>T (p.R377W) alteration is located in exon 3 (coding exon 3) of the APOL3 gene. This alteration results from a C to T substitution at nucleotide position 1129, causing the arginine (R) at amino acid position 377 to be replaced by a tryptophan (W). 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
0.17
BayesDel_addAF
Benign
-0.41
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Benign
0.017
T;.;.;.;.
Eigen
Benign
-0.56
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.75
T;T;.;.;T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.22
T;T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.90
L;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.21
T
PROVEAN
Uncertain
-3.8
D;.;D;D;.
REVEL
Benign
0.077
Sift
Uncertain
0.0010
D;.;D;D;.
Sift4G
Uncertain
0.0030
D;D;D;D;D
Polyphen
1.0
D;.;.;.;D
Vest4
0.24
MVP
0.42
MPC
0.62
ClinPred
0.27
T
GERP RS
-3.5
Varity_R
0.22
gMVP
0.22

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.

Other links and lift over

dbSNP: rs371643988; hg19: chr22-36537328; API