rs11089781

chr22-36160720-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM4 BA1

The ENST00000349314.6(APOL3):c.172C>T(p.Gln58Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 1,614,018 control chromosomes in the GnomAD database, including 1,916 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.061 (1021 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (895 hom.)
• Consequence: APOL3 ENST00000349314.6 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM4: Stoplost variant in ENST00000349314.6 Downstream stopcodon found after 1 codons.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL3	NM_145639.2	c.-139C>T		5_prime_UTR_variant	1/4	ENST00000424878.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL3	ENST00000424878.4	c.-139C>T		5_prime_UTR_variant	1/4	1	NM_145639.2	A2

Frequencies

GnomAD3 genomes AF: 0.0612 AC: 9309 AN: 152016 Hom.: 1020 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0179

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0364

GnomAD3 exomes AF: 0.0158 AC: 3974 AN: 251404 Hom.: 436 AF XY: 0.0113 AC XY: 1531 AN XY: 135866

Gnomad AFR exome AF: 0.222

Gnomad AMR exome AF: 0.00807

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000290

Gnomad OTH exome AF: 0.00685

GnomAD4 exome AF: 0.00607 AC: 8873 AN: 1461884 Hom.: 895 Cov.: 30 AF XY: 0.00517 AC XY: 3758 AN XY: 727242

Gnomad4 AFR exome AF: 0.221

Gnomad4 AMR exome AF: 0.00948

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000261

Gnomad4 OTH exome AF: 0.0118

GnomAD4 genome AF: 0.0612 AC: 9316 AN: 152134 Hom.: 1021 Cov.: 32 AF XY: 0.0591 AC XY: 4400 AN XY: 74398

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.0179

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0360

Alfa AF: 0.0119 Hom.: 233

Bravo AF: 0.0699

ESP6500AA AF: 0.218 AC: 962

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.0200 AC: 2429

Asia WGS AF: 0.00751 AC: 27 AN: 3478

EpiCase AF: 0.000654

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	0.050
Cadd	Benign	1.1
Dann	Uncertain	0.99
Eigen	Benign	0.13
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.062	N
MutationTaster	Benign	4.3e-9	P;P;P;P;P
Vest4		0.026
GERP RS		1.7

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

Other links and lift over

dbSNP: rs11089781; hg19: chr22-36556768; COSMIC: COSV62579650; COSMIC: COSV62579650;