Genetic Variant NM_001917.5:c.279G>A (chr12-108887534-G-A) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001917.5(DAO):c.279G>A(p.Ser93Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 1,613,036 control chromosomes in the GnomAD database, including 9,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 2294 hom., cov: 32)

Exomes 𝑓: 0.086 ( 6958 hom. )

Consequence

DAO
NM_001917.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.816

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 12-108887534-G-A is Benign according to our data. Variant chr12-108887534-G-A is described in ClinVar as [Benign]. Clinvar id is 1279421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.816 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAO	NM_001917.5 link	c.279G>A	p.Ser93Ser	synonymous_variant	Exon 3 of 11	ENST00000228476.8	NP_001908.3	P14920A0A024RBI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000228476.8 link	c.279G>A	p.Ser93Ser	synonymous_variant	Exon 3 of 11	1	NM_001917.5	ENSP00000228476.3		P14920

Frequencies

GnomAD3 genomes

AF:

0.138

AC:

21013

AN:

151826

Hom.:

2284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.0770

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.00290

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.0616

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.0769

Gnomad OTH

AF:

0.124

GnomAD3 exomes

AF:

0.0948

AC:

23843

AN:

251454

Hom.:

1780

AF XY:

0.0966

AC XY:

13134

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.307

Gnomad AMR exome

AF:

0.0570

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.00103

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.0541

Gnomad NFE exome

AF:

0.0795

Gnomad OTH exome

AF:

0.0956

GnomAD4 exome

AF:

0.0862

AC:

125973

AN:

1461092

Hom.:

6958

Cov.:

AF XY:

0.0880

AC XY:

63961

AN XY:

726902

show subpopulations

Gnomad4 AFR exome

AF:

0.315

Gnomad4 AMR exome

AF:

0.0590

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.000630

Gnomad4 SAS exome

AF:

0.157

Gnomad4 FIN exome

AF:

0.0542

Gnomad4 NFE exome

AF:

0.0782

Gnomad4 OTH exome

AF:

0.0937

GnomAD4 genome

AF:

0.139

AC:

21054

AN:

151944

Hom.:

2294

Cov.:

AF XY:

0.136

AC XY:

10121

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.301

Gnomad4 AMR

AF:

0.0768

Gnomad4 ASJ

AF:

0.107

Gnomad4 EAS

AF:

0.00290

Gnomad4 SAS

AF:

0.148

Gnomad4 FIN

AF:

0.0616

Gnomad4 NFE

AF:

0.0769

Gnomad4 OTH

AF:

0.128

Alfa

AF:

0.0909

Hom.:

1223

Bravo

AF:

0.146

Asia WGS

AF:

0.111

AC:

388

AN:

3478

EpiCase

AF:

0.0845

EpiControl

AF:

0.0826

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

DAO-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

5.8

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over