Variant chrX-85074013-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_198450.6(APOOL):c.502G>A(p.Val168Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000562 in 1,157,524 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000054 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000056 ( 0 hom. 16 hem. )

Consequence

APOOL
NM_198450.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.929

Variant links:

Genes affected

APOOL (HGNC:24009): (apolipoprotein O like) This gene encodes a protein which contains an apolipoprotein O superfamily domain. This domain is found on proteins in circulating lipoprotein complexes. [provided by RefSeq, Sep 2011]

APOOL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.061370373).

BP6

Variant X-85074013-G-A is Benign according to our data. Variant chrX-85074013-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2369032.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOOL	NM_198450.6 linkuse as main transcript	c.502G>A	p.Val168Ile	missense_variant	7/9	ENST00000373173.7	NP_940852.3
APOOL	XM_017029272.2 linkuse as main transcript	c.502G>A	p.Val168Ile	missense_variant	7/9		XP_016884761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOOL	ENST00000373173.7 linkuse as main transcript	c.502G>A	p.Val168Ile	missense_variant	7/9	1	NM_198450.6	ENSP00000362268	P1

Frequencies

GnomAD3 genomes

AF:

0.0000540

AC:

AN:

111095

Hom.:

Cov.:

AF XY:

0.0000300

AC XY:

AN XY:

33349

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000113

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000454

AC:

AN:

110049

Hom.:

AF XY:

0.0000298

AC XY:

AN XY:

33517

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000111

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000564

AC:

AN:

1046379

Hom.:

Cov.:

AF XY:

0.0000474

AC XY:

AN XY:

337459

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000274

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000637

Gnomad4 OTH exome

AF:

0.0000453

GnomAD4 genome

AF:

0.0000540

AC:

AN:

111145

Hom.:

Cov.:

AF XY:

0.0000299

AC XY:

AN XY:

33409

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000113

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000160

AC:

ExAC

AF:

0.0000403

AC:

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 14, 2022

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

Benign

0.074

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.57

DANN

Benign

0.24

DEOGEN2

Benign

0.11

T;T

FATHMM_MKL

Benign

0.65

LIST_S2

Benign

0.47

T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.99

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.040

N;.

REVEL

Benign

0.038

Sift

Benign

0.99

T;.

Sift4G

Benign

0.58

T;T

Polyphen

0.0

B;.

Vest4

0.092

MVP

0.082

MPC

0.012

ClinPred

0.011

GERP RS

3.2

Varity_R

0.029

gMVP

0.18

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