Genetic Variant APOLD1:p.Gly13Val (chr12-12786943-G-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP2BP4_Strong

The NM_030817.3(APOLD1):c.38G>T(p.Gly13Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,459,742 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000052 ( 0 hom. )

Consequence

APOLD1
NM_030817.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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: Likely_benign. The variant received -3 ACMG points.

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=0.004500866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
APOLD1	NM_030817.3 link	c.38G>T	p.Gly13Val	missense_variant	Exon 2 of 2	ENST00000356591.5	NP_110444.3	Q96LR9-2A0AVN6
APOLD1	NM_001130415.2 link	c.131G>T	p.Gly44Val	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>T	p.Gly13Val	missense_variant	Exon 2 of 2	1	NM_030817.3	ENSP00000348998.4		Q96LR9-2

Frequencies

GnomAD3 genomes

AF:

0.000513

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00176

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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

GnomAD2 exomes

AF:

0.0000501

AC:

AN:

59844

AF XY:

0.0000284

show subpopulations

Gnomad AFR exome

AF:

0.00242

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:

0.000571

GnomAD4 exome

AF:

0.0000520

AC:

AN:

1307434

Hom.:

Cov.:

AF XY:

0.0000466

AC XY:

AN XY:

644244

show subpopulations

African (AFR)

AF:

0.00153

AC:

AN:

26176

American (AMR)

AF:

0.000133

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:

0.0000143

AC:

AN:

69946

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33466

Middle Eastern (MID)

AF:

0.000484

AC:

AN:

4132

European-Non Finnish (NFE)

AF:

0.00000764

AC:

AN:

1046602

Other (OTH)

AF:

0.000258

AC:

AN:

54254

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.000538

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00185

AC:

AN:

41580

American (AMR)

AF:

0.000196

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

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:

0.0000471

Hom.:

Bravo

AF:

0.000544

ExAC

AF:

0.0000713

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Sep 01, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.131G>T (p.G44V) 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 131, causing the glycine (G) at amino acid position 44 to be replaced by a valine (V). 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

Benign

0.20

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0019

T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.69

T;T

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

L;.

PhyloP100

2.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.88

N;N

REVEL

Benign

0.064

Sift

Benign

0.087

T;T

Sift4G

Benign

0.064

T;T

Polyphen

0.86

P;.

Vest4

0.30

MVP

0.52

ClinPred

0.022

GERP RS

2.6

Varity_R

0.036

gMVP

0.25

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over