rs7980427

chr12-108887534-G-Achr12-108887534-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001917.5(DAO):c.279G>A(p.Ser93=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.816

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]

ACMG classification

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/exons	MANE	UniProt
DAO	NM_001917.5	c.279G>A	p.Ser93=	synonymous_variant	3/11	ENST00000228476.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAO	ENST00000228476.8	c.279G>A	p.Ser93=	synonymous_variant	3/11	1	NM_001917.5	P1

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21013 AN: 151826 Hom.: 2284 Cov.: 32

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

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.: 31 AF XY: 0.0880 AC XY: 63961 AN XY: 726902

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.: 32 AF XY: 0.136 AC XY: 10121 AN XY: 74284

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

DAO-related condition Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 2019

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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

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

Other links and lift over

dbSNP: rs7980427; hg19: chr12-109281310;