chr22-35726784-G-C

Position:

• chr22-35726784-G-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.716G>C​(p.Gly239Ala) 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: -0.138

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=0.07587305).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL5	NM_030642.1	c.716G>C	p.Gly239Ala	missense_variant	3/5	ENST00000249044.2	NP_085145.1
APOL5	XM_006724321.5	c.668G>C	p.Gly223Ala	missense_variant	4/6		XP_006724384.1
APOL5	XM_017028945.3	c.500G>C	p.Gly167Ala	missense_variant	3/5		XP_016884434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL5	ENST00000249044.2	c.716G>C	p.Gly239Ala	missense_variant	3/5	1	NM_030642.1	ENSP00000249044	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 73

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Mar 15, 2024

The c.716G>C (p.G239A) alteration is located in exon 3 (coding exon 3) of the APOL5 gene. This alteration results from a G to C substitution at nucleotide position 716, causing the glycine (G) at amino acid position 239 to be replaced by an alanine (A). 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	0.13
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.54
DANN	Benign	0.95
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-0.95
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.098
Sift	Benign	0.37	T
Sift4G	Benign	0.34	T
Polyphen		0.27	B
Vest4		0.067
MutPred		0.59		Gain of helix (P = 0.0696);
MVP		0.040
MPC		0.22
ClinPred		0.15	T
GERP RS		1.1
Varity_R		0.059
gMVP		0.11

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

LitVar

Other links and lift over

dbSNP: rs1252189673; hg19: chr22-36122831;