22-36160720-G-T

Variant names:

• chr22-36160720-G-T
• rs11089781
• ENST00000349314.7:c.172C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000349314.7(APOL3):​c.172C>A​(p.Gln58Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOL3 ENST00000349314.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09588134).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL3	NM_145639.2	c.-139C>A		5_prime_UTR_variant	Exon 1 of 4	ENST00000424878.4	NP_663614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000424878.4	c.-139C>A		5_prime_UTR_variant	Exon 1 of 4	1	NM_145639.2	ENSP00000415779.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727242

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.55
DANN	Benign	0.68
DEOGEN2	Benign	0.0014	T;.
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.096	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;.
PhyloP100		-1.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.86	N;D
REVEL	Benign	0.036
Sift	Benign	0.92	T;.
Sift4G	Benign	0.44	T;D
Polyphen		0.81	P;.
Vest4		0.21
MutPred		0.31		Gain of ubiquitination at Q58 (P = 0.0045);.;
MVP		0.65
MPC		0.20
ClinPred		0.18	T
GERP RS		1.7
PromoterAI		-0.061	Neutral
Varity_R		0.053
gMVP		0.16
Mutation Taster		=299/1	polymorphism

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

Other links and lift over

dbSNP: rs11089781; hg19: chr22-36556768;