Genetic Variant DAO:c.452+429G>T (chr12-108890702-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001917.5(DAO):c.452+429G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 151,944 control chromosomes in the GnomAD database, including 14,426 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.39 ( 14426 hom., cov: 32)

Consequence

DAO
NM_001917.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.335

Publications

6 publications found

Variant links:

Genes affected

DAO (HGNC:2671): (D-amino acid oxidase) This gene encodes the peroxisomal enzyme D-amino acid oxidase. The enzyme is a flavoprotein which uses flavin adenine dinucleotide (FAD) as its prosthetic group. Its substrates include a wide variety of D-amino acids, but it is inactive on the naturally occurring L-amino acids. Its biological function is not known; it may act as a detoxifying agent which removes D-amino acids that accumulate during aging. In mice, it degrades D-serine, a co-agonist of the NMDA receptor. This gene may play a role in the pathophysiology of schizophrenia. [provided by RefSeq, Jul 2008]

DAO Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, ClinGen

DAO links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001917.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DAO	NM_001917.5	MANE Select	c.452+429G>T	intron	N/A	NP_001908.3
DAO	NM_001413634.1		c.452+429G>T	intron	N/A	NP_001400563.1	P14920
DAO	NM_001413635.1		c.452+429G>T	intron	N/A	NP_001400564.1	A0A0S2Z3J4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DAO	ENST00000228476.8	TSL:1 MANE Select	c.452+429G>T	intron	N/A	ENSP00000228476.3	P14920
DAO	ENST00000551281.5	TSL:1	c.309+3138G>T	intron	N/A	ENSP00000446853.1	A0A0B4J250
DAO	ENST00000547122.5	TSL:1	n.*100+429G>T	intron	N/A	ENSP00000448095.1	A0A0B4J257

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59820

AN:

151826

Hom.:

14383

Cov.:

show subpopulations

Gnomad AFR

AF:

0.645

Gnomad AMI

AF:

0.252

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.540

Gnomad SAS

AF:

0.379

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.403

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.394

AC:

59932

AN:

151944

Hom.:

14426

Cov.:

AF XY:

0.401

AC XY:

29816

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.646

AC:

26751

AN:

41428

American (AMR)

AF:

0.507

AC:

7730

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1043

AN:

3468

East Asian (EAS)

AF:

0.540

AC:

2795

AN:

5174

South Asian (SAS)

AF:

0.379

AC:

1828

AN:

4820

European-Finnish (FIN)

AF:

0.281

AC:

2962

AN:

10540

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.230

AC:

15617

AN:

67944

Other (OTH)

AF:

0.406

AC:

857

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1639

3277

4916

6554

8193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.289

Hom.:

33360

Bravo

AF:

0.425

Asia WGS

AF:

0.446

AC:

1550

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.66

(source)

DANN

Benign

0.26

PhyloP100

-0.34

Mutation Taster

=100/0

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over