22-35726319-G-T

Variant names:

• chr22-35726319-G-T
• rs369534518
• NM_030642.1:c.251G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030642.1(APOL5):​c.251G>T​(p.Arg84Leu) 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. 16/22 in silico tools predict a benign 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. R84Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: APOL5 NM_030642.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• Publications: 4 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06288329).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030642.1. 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
	APOL5	NM_030642.1	MANE Select	c.251G>T	p.Arg84Leu	missense	Exon 3 of 5	NP_085145.1	Q9BWW9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	APOL5	ENST00000249044.2	TSL:1 MANE Select	c.251G>T	p.Arg84Leu	missense	Exon 3 of 5	ENSP00000249044.2	Q9BWW9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.044
DANN	Benign	0.66
DEOGEN2	Benign	0.0022	T
Eigen	Benign	-2.0
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.00063	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.3	L
PhyloP100		-1.9
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.80	N
REVEL	Benign	0.023
Sift	Benign	0.17	T
Sift4G	Benign	0.37	T
Polyphen		0.0020	B
Vest4		0.27
MutPred		0.40		Loss of solvent accessibility (P = 0.0299)
MVP		0.092
MPC		0.25
ClinPred		0.091	T
GERP RS		-4.8
Varity_R		0.062
gMVP		0.075
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

dbSNP: rs369534518; hg19: chr22-36122366;