Genetic Variant NM_030817.3:c.38G>C (chr12-12786943-G-C) – 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>C(p.Gly13Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,459,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000011 ( 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=0.071946025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOLD1	NM_030817.3 link	c.38G>C	p.Gly13Ala	missense_variant	Exon 2 of 2	ENST00000356591.5	NP_110444.3	Q96LR9-2A0AVN6
APOLD1	NM_001130415.2 link	c.131G>C	p.Gly44Ala	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>C	p.Gly13Ala	missense_variant	Exon 2 of 2	1	NM_030817.3	ENSP00000348998.4		Q96LR9-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1307436

Hom.:

Cov.:

AF XY:

0.00000776

AC XY:

AN XY:

644246

show subpopulations

African (AFR)

AF:

0.000115

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:

0.00000955

AC:

AN:

1046602

Other (OTH)

AF:

0.0000184

AC:

AN:

54254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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

AF:

0.0000263

AC:

AN:

152190

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.0000482

AC:

AN:

41458

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.0014

T;.

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.014

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.92

L;.

PhyloP100

2.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.26

N;N

REVEL

Benign

0.012

Sift

Benign

0.23

T;T

Sift4G

Benign

0.28

T;T

Polyphen

0.27

B;.

Vest4

0.10

MutPred

0.32

Gain of helix (P = 0.0496);.;

MVP

0.22

ClinPred

0.13

GERP RS

2.6

Varity_R

0.039

gMVP

0.22

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over