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22-36141764-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_145639.2(APOL3):c.432G>A(p.Thr144=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000476 in 1,614,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00064 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00046 ( 0 hom. )

Consequence

APOL3
NM_145639.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.732
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 Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 22-36141764-C-T is Benign according to our data. Variant chr22-36141764-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 714120.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.732 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
APOL3NM_145639.2 linkuse as main transcriptc.432G>A p.Thr144= synonymous_variant 4/4 ENST00000424878.4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
APOL3ENST00000424878.4 linkuse as main transcriptc.432G>A p.Thr144= synonymous_variant 4/41 NM_145639.2 A2O95236-2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000644
AC:
98
AN:
152202
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00778
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000838
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.000726
AC:
182
AN:
250782
Hom.:
0
AF XY:
0.000671
AC XY:
91
AN XY:
135570
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000724
Gnomad ASJ exome
AF:
0.00657
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.0000463
Gnomad NFE exome
AF:
0.000760
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000459
AC:
671
AN:
1461838
Hom.:
0
Cov.:
36
AF XY:
0.000470
AC XY:
342
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000648
Gnomad4 ASJ exome
AF:
0.00562
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.000400
Gnomad4 OTH exome
AF:
0.000662
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000643
AC:
98
AN:
152320
Hom.:
0
Cov.:
32
AF XY:
0.000564
AC XY:
42
AN XY:
74498
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00778
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000838
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.000934
Hom.:
0
Bravo
AF:
0.000680
EpiCase
AF:
0.000872
EpiControl
AF:
0.000652

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
Cadd
Benign
1.4
Dann
Benign
0.37

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: rs145617479; hg19: chr22-36537812; COSMIC: COSV104666552; COSMIC: COSV104666552; API