22-36141489-A-G

Variant summary

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

The NM_145639.2(APOL3):ā€‹c.707T>Cā€‹(p.Leu236Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,614,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000072 ( 0 hom., cov: 32)
Exomes š‘“: 0.000029 ( 0 hom. )

Consequence

APOL3
NM_145639.2 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.21
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=0.10592687).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
APOL3NM_145639.2 linkuse as main transcriptc.707T>C p.Leu236Pro missense_variant 4/4 ENST00000424878.4 NP_663614.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APOL3ENST00000424878.4 linkuse as main transcriptc.707T>C p.Leu236Pro missense_variant 4/41 NM_145639.2 ENSP00000415779 A2O95236-2

Frequencies

GnomAD3 genomes
AF:
0.0000723
AC:
11
AN:
152200
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000437
AC:
11
AN:
251430
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135882
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:
0.0000879
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461888
Hom.:
0
Cov.:
36
AF XY:
0.0000371
AC XY:
27
AN XY:
727246
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:
0.0000374
Gnomad4 NFE exome
AF:
0.0000252
Gnomad4 OTH exome
AF:
0.000199
GnomAD4 genome
AF:
0.0000723
AC:
11
AN:
152200
Hom.:
0
Cov.:
32
AF XY:
0.0000538
AC XY:
4
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000676
Hom.:
0
Bravo
AF:
0.0000151
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.000218
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 GeneticsSep 20, 2023The c.920T>C (p.L307P) alteration is located in exon 3 (coding exon 3) of the APOL3 gene. This alteration results from a T to C substitution at nucleotide position 920, causing the leucine (L) at amino acid position 307 to be replaced by a proline (P). 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
0.091
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
0.073
DANN
Benign
0.82
DEOGEN2
Benign
0.0042
T;.;.;.;.
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.4
FATHMM_MKL
Benign
0.024
N
LIST_S2
Benign
0.15
T;T;.;.;T
M_CAP
Benign
0.0041
T
MetaRNN
Benign
0.11
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.6
L;.;.;.;.
MutationTaster
Benign
1.0
N;N;N;N;N
PrimateAI
Benign
0.21
T
PROVEAN
Uncertain
-2.4
N;.;D;D;.
REVEL
Benign
0.069
Sift
Benign
0.053
T;.;D;D;.
Sift4G
Benign
0.10
T;T;T;T;T
Polyphen
0.74
P;.;.;.;P
Vest4
0.082
MVP
0.12
MPC
0.46
ClinPred
0.078
T
GERP RS
-4.9
Varity_R
0.25
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.

Other links and lift over

dbSNP: rs372981691; hg19: chr22-36537537; API