12-108878275-C-T

Position:

• chr12-108878275-C-T

Variant summary

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

The ENST00000551281.5(DAO):​c.-9-6723C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 151,884 control chromosomes in the GnomAD database, including 33,799 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 0.66 (33799 hom., cov: 30)
• Consequence: DAO ENST00000551281.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.271

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000551281.5	c.-9-6723C>T		intron_variant		1		ENSP00000446853
DAO	ENST00000548052.5	n.349-1288C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100407 AN: 151766 Hom.: 33754 Cov.: 30

Gnomad AFR AF: 0.759

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.726

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.796

Gnomad SAS AF: 0.709

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.662 AC: 100513 AN: 151884 Hom.: 33799 Cov.: 30 AF XY: 0.666 AC XY: 49417 AN XY: 74226

Gnomad4 AFR AF: 0.759

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.796

Gnomad4 SAS AF: 0.710

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.655

Alfa AF: 0.610 Hom.: 20834

Bravo AF: 0.678

Asia WGS AF: 0.714 AC: 2480 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.33
DANN	Benign	0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4623951; hg19: chr12-109272051;