22-35726309-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_030642.1(APOL5):c.241G>A(p.Glu81Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00275 in 1,614,164 control chromosomes in the GnomAD database, including 83 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.013 (37 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (46 hom.)
• Consequence: APOL5 NM_030642.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.74

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0020682514).
• BP6: Variant 22-35726309-G-A is Benign according to our data. Variant chr22-35726309-G-A is described in ClinVar as [Benign]. Clinvar id is 780637.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0132 (2017/152296) while in subpopulation AFR AF= 0.0448 (1863/41550). AF 95% confidence interval is 0.0431. There are 37 homozygotes in gnomad4. There are 957 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
APOL5	NM_030642.1	c.241G>A	p.Glu81Lys	missense_variant	3/5	ENST00000249044.2
APOL5	XM_006724321.5	c.193G>A	p.Glu65Lys	missense_variant	4/6
APOL5	XM_017028945.3	c.25G>A	p.Glu9Lys	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
APOL5	ENST00000249044.2	c.241G>A	p.Glu81Lys	missense_variant	3/5	1	NM_030642.1	P1

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2003 AN: 152178 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.0446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00733

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00764

GnomAD3 exomes AF: 0.00360 AC: 906 AN: 251368 Hom.: 20 AF XY: 0.00285 AC XY: 387 AN XY: 135868

Gnomad AFR exome AF: 0.0459

Gnomad AMR exome AF: 0.00243

Gnomad ASJ exome AF: 0.00109

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000396

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00166 AC: 2429 AN: 1461868 Hom.: 46 Cov.: 31 AF XY: 0.00146 AC XY: 1065 AN XY: 727232

Gnomad4 AFR exome AF: 0.0479

Gnomad4 AMR exome AF: 0.00275

Gnomad4 ASJ exome AF: 0.000650

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.000112

Gnomad4 NFE exome AF: 0.000351

Gnomad4 OTH exome AF: 0.00401

GnomAD4 genome AF: 0.0132 AC: 2017 AN: 152296 Hom.: 37 Cov.: 32 AF XY: 0.0129 AC XY: 957 AN XY: 74466

Gnomad4 AFR AF: 0.0448

Gnomad4 AMR AF: 0.00732

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000323

Gnomad4 OTH AF: 0.00756

Alfa AF: 0.00292 Hom.: 11

Bravo AF: 0.0150

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0381 AC: 168

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.00414 AC: 503

Asia WGS AF: 0.00520 AC: 18 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 06, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.69
Cadd	Benign	16
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0021	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.61	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.019
Sift	Benign	0.068	T
Sift4G	Benign	0.090	T
Polyphen		0.14	B
Vest4		0.24
MVP		0.12
MPC		0.37
ClinPred		0.0098	T
GERP RS		0.40
Varity_R		0.12
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs5999985; hg19: chr22-36122356;