22-36141715-C-T

Variant names:

• chr22-36141715-C-T
• rs61741884
• NM_145639.2:c.481G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_145639.2(APOL3):​c.481G>A​(p.Val161Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0537 in 1,613,978 control chromosomes in the GnomAD database, including 2,721 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 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: 𝑓 0.046 (215 hom., cov: 32)
  • Exomes 𝑓: 0.054 (2506 hom.)
• Consequence: APOL3 NM_145639.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005245805).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.063 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145639.2. 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.481G>A	p.Val161Met	missense	Exon 4 of 4	NP_663614.1	O95236-2
	APOL3	NM_145640.2		c.694G>A	p.Val232Met	missense	Exon 3 of 3	NP_663615.1	O95236-1
	APOL3	NM_001393587.1		c.484G>A	p.Val162Met	missense	Exon 5 of 5	NP_001380516.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL3	ENST00000424878.4	TSL:1 MANE Select	c.481G>A	p.Val161Met	missense	Exon 4 of 4	ENSP00000415779.3	O95236-2
	APOL3	ENST00000349314.7	TSL:1	c.694G>A	p.Val232Met	missense	Exon 3 of 3	ENSP00000344577.2	O95236-1
	APOL3	ENST00000361710.6	TSL:1	c.94G>A	p.Val32Met	missense	Exon 4 of 4	ENSP00000355164.2	O95236-3

Frequencies

GnomAD3 genomes AF: 0.0463 AC: 7053 AN: 152192 Hom.: 215 Cov.: 32

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0666

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0847

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0630

GnomAD2 exomes AF: 0.0438 AC: 10958 AN: 250398 AF XY: 0.0449

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.0399

Gnomad ASJ exome AF: 0.0259

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0776

Gnomad NFE exome AF: 0.0595

Gnomad OTH exome AF: 0.0576

GnomAD4 exome AF: 0.0544 AC: 79554 AN: 1461668 Hom.: 2506 Cov.: 36 AF XY: 0.0535 AC XY: 38923 AN XY: 727126

African (AFR) AF: 0.0107 AC: 359 AN: 33480

American (AMR) AF: 0.0413 AC: 1849 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0284 AC: 743 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.0132 AC: 1141 AN: 86248

European-Finnish (FIN) AF: 0.0753 AC: 4011 AN: 53272

Middle Eastern (MID) AF: 0.0636 AC: 367 AN: 5768

European-Non Finnish (NFE) AF: 0.0610 AC: 67800 AN: 1111964

Other (OTH) AF: 0.0544 AC: 3283 AN: 60382

GnomAD4 genome AF: 0.0463 AC: 7046 AN: 152310 Hom.: 215 Cov.: 32 AF XY: 0.0465 AC XY: 3463 AN XY: 74478

African (AFR) AF: 0.0124 AC: 516 AN: 41572

American (AMR) AF: 0.0663 AC: 1015 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0245 AC: 85 AN: 3468

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.00994 AC: 48 AN: 4828

European-Finnish (FIN) AF: 0.0847 AC: 898 AN: 10606

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0634 AC: 4315 AN: 68030

Other (OTH) AF: 0.0619 AC: 131 AN: 2116

Alfa AF: 0.0531 Hom.: 554

Bravo AF: 0.0432

TwinsUK AF: 0.0639 AC: 237

ALSPAC AF: 0.0576 AC: 222

ESP6500AA AF: 0.0109 AC: 48

ESP6500EA AF: 0.0631 AC: 543

ExAC AF: 0.0414 AC: 5030

Asia WGS AF: 0.00924 AC: 32 AN: 3478

EpiCase AF: 0.0660

EpiControl AF: 0.0651

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.1
DANN	Benign	0.96
DEOGEN2	Benign	0.060	T
Eigen	Benign	-0.40
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		-0.10
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.094
Sift	Uncertain	0.029	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.93	P
Vest4		0.18
MPC		0.50
ClinPred		0.045	T
GERP RS		-1.5
Varity_R		0.086
gMVP		0.56
Mutation Taster		=100/0	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: rs61741884; hg19: chr22-36537763; COSMIC: COSV62580663; COSMIC: COSV62580663;