rs2076672

Positions:

• chr22-35727036-C-T

Variant summary

Our verdict is Benign. Variant got -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. 12/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL5	NM_030642.1	c.968C>T	p.Thr323Met	missense_variant	3/5	ENST00000249044.2	NP_085145.1
APOL5	XM_006724321.5	c.920C>T	p.Thr307Met	missense_variant	4/6		XP_006724384.1
APOL5	XM_017028945.3	c.752C>T	p.Thr251Met	missense_variant	3/5		XP_016884434.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL5	ENST00000249044.2	c.968C>T	p.Thr323Met	missense_variant	3/5	1	NM_030642.1	ENSP00000249044.2

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

GnomAD3 exomes AF: 0.227 AC: 56946 AN: 250780 Hom.: 6909 AF XY: 0.229 AC XY: 31116 AN XY: 135608

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 SAS exome AF: 0.183

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

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.267

Gnomad4 EAS exome AF: 0.0918

Gnomad4 SAS exome AF: 0.181

Gnomad4 FIN exome AF: 0.234

Gnomad4 NFE exome AF: 0.267

Gnomad4 OTH exome AF: 0.242

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

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.249

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.0836

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.225

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.234

Alfa AF: 0.255 Hom.: 12564

Bravo AF: 0.209

TwinsUK AF: 0.267 AC: 989

ALSPAC AF: 0.265 AC: 1021

ESP6500AA AF: 0.119 AC: 523

ESP6500EA AF: 0.263 AC: 2264

ExAC AF: 0.225 AC: 27361

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 v4.3

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
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.069
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.056
MPC		0.68
ClinPred		0.024	T
GERP RS		1.8
Varity_R		0.14
gMVP		0.26

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: rs2076672; hg19: chr22-36123083; COSMIC: COSV50766333;