rs767965613

Variant names:

• chr22-36141295-C-G
• NM_145639.2:c.901G>C

Your query was ambiguous. Multiple possible variants found:

• chr22-36141295-C-G
• chr22-36141295-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_145639.2(APOL3):​c.901G>C​(p.Ala301Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A301T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: APOL3 NM_145639.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.73

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_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOL3	NM_145639.2	c.901G>C	p.Ala301Pro	missense_variant	Exon 4 of 4	ENST00000424878.4	NP_663614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOL3	ENST00000424878.4	c.901G>C	p.Ala301Pro	missense_variant	Exon 4 of 4	1	NM_145639.2	ENSP00000415779.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461888 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 727244

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.82
BayesDel_addAF	Uncertain	0.023	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T;.;.;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.86	D;T;.;.;D
M_CAP	Benign	0.025	T
MetaRNN	Pathogenic	0.94	D;D;D;D;D
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.8	M;.;.;.;.
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-4.5	D;.;D;D;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.0020	D;.;D;D;.
Sift4G	Uncertain	0.0050	D;D;D;D;D
Polyphen		1.0	D;.;.;.;D
Vest4		0.53
MutPred		0.82		Loss of helix (P = 0.0167);.;.;.;.;
MVP		0.39
MPC		0.74
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.95
gMVP		0.77

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-36537343;