12-12787524-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000356591.5(APOLD1):​c.619G>A​(p.Glu207Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

APOLD1
ENST00000356591.5 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.95
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33233517).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
APOLD1NM_030817.3 linkuse as main transcriptc.619G>A p.Glu207Lys missense_variant 2/2 ENST00000356591.5 NP_110444.3
APOLD1NM_001130415.2 linkuse as main transcriptc.712G>A p.Glu238Lys missense_variant 2/2 NP_001123887.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
APOLD1ENST00000356591.5 linkuse as main transcriptc.619G>A p.Glu207Lys missense_variant 2/21 NM_030817.3 ENSP00000348998 P1Q96LR9-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250340
Hom.:
0
AF XY:
0.00000737
AC XY:
1
AN XY:
135726
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000544
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461654
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727126
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsAug 01, 2022The c.712G>A (p.E238K) alteration is located in exon 2 (coding exon 2) of the APOLD1 gene. This alteration results from a G to A substitution at nucleotide position 712, causing the glutamic acid (E) at amino acid position 238 to be replaced by a lysine (K). 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
0.44
BayesDel_addAF
Benign
-0.032
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0052
T;.
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.46
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Uncertain
0.92
D;D
M_CAP
Benign
0.0088
T
MetaRNN
Benign
0.33
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.0
L;.
MutationTaster
Benign
0.95
D;D
PrimateAI
Uncertain
0.62
T
PROVEAN
Benign
-0.25
N;N
REVEL
Benign
0.13
Sift
Benign
0.13
T;T
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.91
P;.
Vest4
0.58
MutPred
0.47
Gain of ubiquitination at E238 (P = 0.0094);.;
MVP
0.68
ClinPred
0.87
D
GERP RS
5.4
Varity_R
0.34
gMVP
0.35

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.

Other links and lift over

dbSNP: rs1264834503; hg19: chr12-12940458; API