dbSNP rs765222554: APOLD1:p.Gly13Glu (chr12-12786943-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_030817.3(APOLD1):c.38G>A(p.Gly13Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000459 in 1,307,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G13V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000046 ( 0 hom. )

Consequence

APOLD1
NM_030817.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.96

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 1 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 0.44893 (below the threshold of 3.09). Trascript score misZ: -2.3159 (below the threshold of 3.09).

BP4

Computational evidence support a benign effect (MetaRNN=0.09472498).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOLD1	NM_030817.3 link	c.38G>A	p.Gly13Glu	missense_variant	Exon 2 of 2	ENST00000356591.5	NP_110444.3	Q96LR9-2A0AVN6
APOLD1	NM_001130415.2 link	c.131G>A	p.Gly44Glu	missense_variant	Exon 2 of 2		NP_001123887.1	Q96LR9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
APOLD1	ENST00000356591.5 link	c.38G>A	p.Gly13Glu	missense_variant	Exon 2 of 2	1	NM_030817.3	ENSP00000348998.4		Q96LR9-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

59844

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000459

AC:

AN:

1307436

Hom.:

Cov.:

AF XY:

0.00000310

AC XY:

AN XY:

644246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26176

American (AMR)

AF:

0.00

AC:

AN:

22492

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22162

East Asian (EAS)

AF:

0.00

AC:

AN:

28204

South Asian (SAS)

AF:

0.00

AC:

AN:

69948

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33466

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000478

AC:

AN:

1046602

Other (OTH)

AF:

0.0000184

AC:

AN:

54254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0039

T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.68

T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.095

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.6

L;.

PhyloP100

2.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.96

N;N

REVEL

Benign

0.057

Sift

Benign

0.40

T;T

Sift4G

Benign

0.24

T;T

Polyphen

0.76

P;.

Vest4

0.30

MutPred

0.37

Loss of MoRF binding (P = 0.0582);.;

MVP

0.40

ClinPred

0.14

GERP RS

2.6

Varity_R

0.026

gMVP

0.36

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over