22-35726786-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_030642.1(APOL5):c.718A>C(p.Ile240Leu) 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. 15/21 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: APOL5 NM_030642.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0700

Genes affected

APOL5 (HGNC:14869): (apolipoprotein L5) This gene is a member of the apolipoprotein L gene family. The encoded protein is found in the cytoplasm, where it may affect the movement of lipids or allow the binding of lipids to organelles. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23039103).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL5	NM_030642.1	c.718A>C	p.Ile240Leu	missense_variant	3/5	ENST00000249044.2
APOL5	XM_006724321.5	c.670A>C	p.Ile224Leu	missense_variant	4/6
APOL5	XM_017028945.3	c.502A>C	p.Ile168Leu	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL5	ENST00000249044.2	c.718A>C	p.Ile240Leu	missense_variant	3/5	1	NM_030642.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 16, 2024

The c.718A>C (p.I240L) alteration is located in exon 3 (coding exon 3) of the APOL5 gene. This alteration results from a A to C substitution at nucleotide position 718, causing the isoleucine (I) at amino acid position 240 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
Cadd	Benign	1.6
Dann	Benign	0.84
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.62	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.065
Sift	Benign	0.10	T
Sift4G	Benign	0.17	T
Polyphen		0.017	B
Vest4		0.16
MutPred		0.78		Loss of methylation at K241 (P = 0.0725);
MVP		0.061
MPC		0.20
ClinPred		0.076	T
GERP RS		-6.3
Varity_R		0.11
gMVP		0.18

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: chr22-36122833;