Variant 22-35658815-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_030641.4(APOL6):c.251C>T(p.Thr84Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00053 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 0 hom. )

Consequence

APOL6
NM_030641.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.875

Variant links:

Genes affected

APOL6 (HGNC:14870): (apolipoprotein L6) 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]

APOL6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0067358017).

BP6

Variant 22-35658815-C-T is Benign according to our data. Variant chr22-35658815-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2345823.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOL6	NM_030641.4 linkuse as main transcript	c.251C>T	p.Thr84Ile	missense_variant	3/3	ENST00000409652.5	NP_085144.1	Q9BWW8B3KTP4
APOL6	XM_011530392.4 linkuse as main transcript	c.251C>T	p.Thr84Ile	missense_variant	4/4		XP_011528694.1	Q9BWW8B3KTP4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOL6	ENST00000409652.5 linkuse as main transcript	c.251C>T	p.Thr84Ile	missense_variant	3/3	1	NM_030641.4	ENSP00000386280.3		Q9BWW8

Frequencies

GnomAD3 genomes

AF:

0.000979

AC:

149

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00318

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000705

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000765

AC:

192

AN:

250996

Hom.:

AF XY:

0.000811

AC XY:

110

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00165

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000556

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.000483

AC:

706

AN:

1461886

Hom.:

Cov.:

AF XY:

0.000523

AC XY:

380

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00233

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000661

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000358

Gnomad4 OTH exome

AF:

0.00134

GnomAD4 genome

AF:

0.000985

AC:

150

AN:

152326

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00115

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00318

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000706

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000682

Hom.:

Bravo

AF:

0.00121

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000758

AC:

EpiCase

AF:

0.000545

EpiControl

AF:

0.000889

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 17, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.55

DANN

Benign

0.94

DEOGEN2

Benign

0.12

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0056

LIST_S2

Benign

0.48

M_CAP

Benign

0.0015

MetaRNN

Benign

0.0067

MetaSVM

Benign

-0.91

MutationAssessor

Uncertain

2.1

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.2

REVEL

Benign

0.093

Sift

Benign

0.085

Sift4G

Benign

0.46

Polyphen

0.0070

Vest4

0.052

MVP

0.17

MPC

0.18

ClinPred

0.0084

GERP RS

-2.2

Varity_R

0.039

gMVP

0.38

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over