Variant X-85067172-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_198450.6(APOOL):c.440T>C(p.Leu147Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000345 in 1,160,150 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000019 ( 0 hom. 1 hem. )

Consequence

APOOL
NM_198450.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
APOOL	NM_198450.6 linkuse as main transcript	c.440T>C	p.Leu147Ser	missense_variant	6/9	ENST00000373173.7	NP_940852.3
APOOL	XM_017029272.2 linkuse as main transcript	c.440T>C	p.Leu147Ser	missense_variant	6/9		XP_016884761.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOOL	ENST00000373173.7 linkuse as main transcript	c.440T>C	p.Leu147Ser	missense_variant	6/9	1	NM_198450.6	ENSP00000362268	P1

Frequencies

GnomAD3 genomes

AF:

0.0000179

AC:

AN:

111624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33790

show subpopulations

Gnomad AFR

AF:

0.0000325

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:

0.00

Gnomad OTH

AF:

0.000664

GnomAD4 exome

AF:

0.00000191

AC:

AN:

1048526

Hom.:

Cov.:

AF XY:

0.00000295

AC XY:

AN XY:

339150

show subpopulations

Gnomad4 AFR exome

AF:

0.0000401

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000123

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000179

AC:

AN:

111624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33790

show subpopulations

Gnomad4 AFR

AF:

0.0000325

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:

0.00

Gnomad4 OTH

AF:

0.000664

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2022

The c.440T>C (p.L147S) alteration is located in exon 6 (coding exon 6) of the APOOL gene. This alteration results from a T to C substitution at nucleotide position 440, causing the leucine (L) at amino acid position 147 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.59

D;.;T

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.57

T;T;T

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.62

D;D;D

MetaSVM

Uncertain

-0.26

MutationTaster

Benign

0.92

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-4.0

D;.;.

REVEL

Uncertain

0.30

Sift

Uncertain

0.0060

D;.;.

Sift4G

Uncertain

0.0090

D;D;D

Polyphen

0.98

D;.;.

Vest4

0.53

MutPred

0.76

Gain of catalytic residue at L147 (P = 0.0099);.;Gain of catalytic residue at L147 (P = 0.0099);

MVP

0.62

MPC

0.043

ClinPred

0.97

GERP RS

4.6

Varity_R

0.49

gMVP

0.67

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