22-35727036-C-T

Variant names:

• chr22-35727036-C-T
• rs2076672
• NM_030642.1:c.968C>T
• APOL5 p.Thr323Met

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030642.1(APOL5):​c.968C>T​(p.Thr323Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 1,613,720 control chromosomes in the GnomAD database, including 51,208 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3745 hom., cov: 32)
  • Exomes 𝑓: 0.25 (47463 hom.)
• Consequence: APOL5 NM_030642.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 26 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0056617856).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

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.968C>T	p.Thr323Met	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.968C>T	p.Thr323Met	missense	Exon 3 of 5	ENSP00000249044.2	Q9BWW9

Frequencies

GnomAD3 genomes AF: 0.211 AC: 32032 AN: 152014 Hom.: 3741 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0830

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.236

GnomAD2 exomes AF: 0.227 AC: 56946 AN: 250780 AF XY: 0.229

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.243

Gnomad ASJ exome AF: 0.264

Gnomad EAS exome AF: 0.0828

Gnomad FIN exome AF: 0.230

Gnomad NFE exome AF: 0.269

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.251 AC: 366243 AN: 1461588 Hom.: 47463 Cov.: 82 AF XY: 0.249 AC XY: 180913 AN XY: 727112

African (AFR) AF: 0.114 AC: 3810 AN: 33478

American (AMR) AF: 0.244 AC: 10917 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.267 AC: 6984 AN: 26136

East Asian (EAS) AF: 0.0918 AC: 3645 AN: 39698

South Asian (SAS) AF: 0.181 AC: 15577 AN: 86254

European-Finnish (FIN) AF: 0.234 AC: 12447 AN: 53244

Middle Eastern (MID) AF: 0.268 AC: 1541 AN: 5742

European-Non Finnish (NFE) AF: 0.267 AC: 296699 AN: 1111952

Other (OTH) AF: 0.242 AC: 14623 AN: 60380

GnomAD4 genome AF: 0.211 AC: 32046 AN: 152132 Hom.: 3745 Cov.: 32 AF XY: 0.209 AC XY: 15502 AN XY: 74344

African (AFR) AF: 0.117 AC: 4842 AN: 41532

American (AMR) AF: 0.249 AC: 3803 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3468

East Asian (EAS) AF: 0.0836 AC: 432 AN: 5166

South Asian (SAS) AF: 0.165 AC: 796 AN: 4820

European-Finnish (FIN) AF: 0.225 AC: 2377 AN: 10580

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18118 AN: 67972

Other (OTH) AF: 0.234 AC: 495 AN: 2116

Alfa AF: 0.248 Hom.: 16462

Bravo AF: 0.209

Asia WGS AF: 0.136 AC: 475 AN: 3478

EpiCase AF: 0.267

EpiControl AF: 0.276

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.055	N
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		1.1
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.069
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Varity_R		0.14
gMVP		0.26
Mutation Taster		=96/4	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2076672;

hg19: chr22-36123083;

COSMIC: COSV50766333;