rs11089781

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr22-36160720-G-A
• chr22-36160720-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_145640.2(APOL3):​c.172C>T​(p.Gln58*) 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 NM_145640.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59
• Publications: 13 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: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145640.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	NM_145639.2	MANE Select	c.-139C>T		5_prime_UTR	Exon 1 of 4	NP_663614.1
	APOL3	NM_145640.2		c.172C>T	p.Gln58*	stop_gained	Exon 1 of 3	NP_663615.1
	APOL3	NM_001393587.1		c.-672C>T		5_prime_UTR	Exon 1 of 5	NP_001380516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	ENST00000349314.7	TSL:1	c.172C>T	p.Gln58*	stop_gained	Exon 1 of 3	ENSP00000344577.2
	APOL3	ENST00000531095.1	TSL:1	c.64C>T	p.Gln22*	stop_gained	Exon 1 of 2	ENSP00000432271.1
	APOL3	ENST00000424878.4	TSL:1 MANE Select	c.-139C>T		5_prime_UTR	Exon 1 of 4	ENSP00000415779.3

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

GnomAD2 exomes AF: 0.0158 AC: 3974 AN: 251404 AF XY: 0.0113

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 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

African (AFR) AF: 0.221 AC: 7394 AN: 33478

American (AMR) AF: 0.00948 AC: 424 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

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

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86258

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

Middle Eastern (MID) AF: 0.00433 AC: 25 AN: 5768

European-Non Finnish (NFE) AF: 0.000261 AC: 290 AN: 1112008

Other (OTH) AF: 0.0118 AC: 715 AN: 60396

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

African (AFR) AF: 0.215 AC: 8935 AN: 41470

American (AMR) AF: 0.0179 AC: 273 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 67976

Other (OTH) AF: 0.0360 AC: 76 AN: 2110

Alfa AF: 0.0231 Hom.: 700

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 v4.9

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
PhyloP100		-1.6
Vest4		0.026
GERP RS		1.7
PromoterAI		-0.20	Neutral
Mutation Taster		=182/18	polymorphism (auto)

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; COSMIC: COSV62579650; COSMIC: COSV62579650;