Variant 12-12787300-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030817.3(APOLD1):c.395G>T(p.Arg132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,458,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

APOLD1
NM_030817.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Variant links:

Genes affected

APOLD1 (HGNC:25268): (apolipoprotein L domain containing 1) APOLD1 is an endothelial cell early response protein that may play a role in regulation of endothelial cell signaling and vascular function (Regard et al., 2004 [PubMed 15102925]).[supplied by OMIM, Dec 2008]

APOLD1 links:

APOLD1 (HGNC:):

APOLD1 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
APOLD1	NM_030817.3 linkuse as main transcript	c.395G>T	p.Arg132Leu	missense_variant	2/2	ENST00000356591.5	NP_110444.3	Q96LR9-2A0AVN6
APOLD1	NM_001130415.2 linkuse as main transcript	c.488G>T	p.Arg163Leu	missense_variant	2/2		NP_001123887.1	Q96LR9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
APOLD1	ENST00000356591.5 linkuse as main transcript	c.395G>T	p.Arg132Leu	missense_variant	2/2	1	NM_030817.3	ENSP00000348998.4		Q96LR9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000403

AC:

AN:

248252

Hom.:

AF XY:

0.00000745

AC XY:

AN XY:

134274

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:

0.00000891

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1458886

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000569

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

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

Apr 07, 2023

The c.488G>T (p.R163L) alteration is located in exon 2 (coding exon 2) of the APOLD1 gene. This alteration results from a G to T substitution at nucleotide position 488, causing the arginine (R) at amino acid position 163 to be replaced by a leucine (L). 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

0.35

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

T;.

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.018

MetaRNN

Uncertain

0.52

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;.

PrimateAI

Uncertain

0.49

PROVEAN

Uncertain

-2.8

D;D

REVEL

Benign

0.13

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.024

D;D

Polyphen

0.99

D;.

Vest4

0.59

MutPred

0.52

Gain of catalytic residue at R163 (P = 0.001);.;

MVP

0.60

ClinPred

0.96

GERP RS

5.3

Varity_R

0.39

gMVP

0.48

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