12-108888108-G-A

Position:

• chr12-108888108-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001917.5(DAO):​c.309+544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,046 control chromosomes in the GnomAD database, including 10,127 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 0.34 (10127 hom., cov: 32)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAO	NM_001917.5	c.309+544G>A		intron_variant		ENST00000228476.8	NP_001908.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000228476.8	c.309+544G>A		intron_variant		1	NM_001917.5	ENSP00000228476.3

Frequencies

GnomAD3 genomes AF: 0.342 AC: 51994 AN: 151928 Hom.: 10108 Cov.: 32

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.253

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.357

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

GnomAD4 genome AF: 0.342 AC: 52070 AN: 152046 Hom.: 10127 Cov.: 32 AF XY: 0.351 AC XY: 26063 AN XY: 74316

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.300

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.360

Alfa AF: 0.281 Hom.: 907

Bravo AF: 0.366

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.035
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs3918346; hg19: chr12-109281884;