22-36141756-G-A

Variant names:

• chr22-36141756-G-A
• NM_145639.2:c.440C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_145639.2(APOL3):​c.440C>T​(p.Ala147Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOL3 NM_145639.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.12
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32971814).

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.440C>T	p.Ala147Val	missense	Exon 4 of 4	NP_663614.1	O95236-2
	APOL3	NM_145640.2		c.653C>T	p.Ala218Val	missense	Exon 3 of 3	NP_663615.1	O95236-1
	APOL3	NM_001393587.1		c.443C>T	p.Ala148Val	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.440C>T	p.Ala147Val	missense	Exon 4 of 4	ENSP00000415779.3	O95236-2
	APOL3	ENST00000349314.7	TSL:1	c.653C>T	p.Ala218Val	missense	Exon 3 of 3	ENSP00000344577.2	O95236-1
	APOL3	ENST00000361710.6	TSL:1	c.53C>T	p.Ala18Val	missense	Exon 4 of 4	ENSP00000355164.2	O95236-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.0020
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.23	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.33	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.47	N
PhyloP100		-3.1
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.040
Sift	Benign	0.59	T
Sift4G	Benign	0.37	T
Polyphen		0.76	P
Vest4		0.031
MutPred		0.44		Gain of sheet (P = 0.1208)
MVP		0.14
MPC		0.53
ClinPred		0.17	T
GERP RS		-1.9
Varity_R		0.048
gMVP		0.27
Mutation Taster		=100/0	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

hg19: chr22-36537804;