chr22-36141750-G-A
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_145639.2(APOL3):c.446C>T(p.Thr149Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,614,122 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.012 ( 42 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 42 hom. )
Consequence
APOL3
NM_145639.2 missense
NM_145639.2 missense
Scores
1
2
15
Clinical Significance
Conservation
PhyloP100: 0.0630
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0046978593).
BP6
?
Variant 22-36141750-G-A is Benign according to our data. Variant chr22-36141750-G-A is described in ClinVar as [Benign]. Clinvar id is 784420.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1865/152330) while in subpopulation AFR AF= 0.0425 (1768/41578). AF 95% confidence interval is 0.0409. There are 42 homozygotes in gnomad4. There are 870 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 42 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
APOL3 | NM_145639.2 | c.446C>T | p.Thr149Ile | missense_variant | 4/4 | ENST00000424878.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
APOL3 | ENST00000424878.4 | c.446C>T | p.Thr149Ile | missense_variant | 4/4 | 1 | NM_145639.2 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0122 AC: 1860AN: 152212Hom.: 42 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00333 AC: 834AN: 250644Hom.: 10 AF XY: 0.00236 AC XY: 320AN XY: 135506
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GnomAD4 exome AF: 0.00136 AC: 1994AN: 1461792Hom.: 42 Cov.: 36 AF XY: 0.00120 AC XY: 876AN XY: 727200
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GnomAD4 genome ? AF: 0.0122 AC: 1865AN: 152330Hom.: 42 Cov.: 32 AF XY: 0.0117 AC XY: 870AN XY: 74500
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ESP6500AA
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Apr 16, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
DEOGEN2
Benign
T;.;.;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;.;.;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;.;.
MutationTaster
Benign
N;N;N;N;N
PrimateAI
Benign
T
PROVEAN
Uncertain
N;.;N;N;.
REVEL
Benign
Sift
Benign
T;.;T;T;.
Sift4G
Benign
T;T;T;T;T
Polyphen
P;.;.;.;P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at