chr22-35726556-C-A

Position:

• chr22-35726556-C-A

Variant summary

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

The NM_030642.1(APOL5):​c.488C>A​(p.Ala163Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: APOL5 NM_030642.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.199

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL5	NM_030642.1	c.488C>A	p.Ala163Glu	missense_variant	3/5	ENST00000249044.2	NP_085145.1
APOL5	XM_006724321.5	c.440C>A	p.Ala147Glu	missense_variant	4/6		XP_006724384.1
APOL5	XM_017028945.3	c.272C>A	p.Ala91Glu	missense_variant	3/5		XP_016884434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL5	ENST00000249044.2	c.488C>A	p.Ala163Glu	missense_variant	3/5	1	NM_030642.1	ENSP00000249044	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461880 Hom.: 0 Cov.: 73 AF XY: 0.00000275 AC XY: 2 AN XY: 727240

Gnomad4 AFR exome AF: 0.00

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

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

May 15, 2024

The c.488C>A (p.A163E) alteration is located in exon 3 (coding exon 3) of the APOL5 gene. This alteration results from a C to A substitution at nucleotide position 488, causing the alanine (A) at amino acid position 163 to be replaced by a glutamic acid (E). 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	0.32
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	10
DANN	Benign	0.90
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0084	T
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.92	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.13
Sift	Benign	0.17	T
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.42
MutPred		0.79		Gain of solvent accessibility (P = 9e-04);
MVP		0.15
MPC		0.67
ClinPred		0.51	D
GERP RS		-0.84
Varity_R		0.31
gMVP		0.84

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: chr22-36122603;