NM_172370.5:c.281+6583C>A

Variant names:

• chr13-105479268-C-A
• rs9519688
• NM_172370.5:c.281+6583C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172370.5(DAOA):​c.281+6583C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,044 control chromosomes in the GnomAD database, including 5,453 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 0.26 (5453 hom., cov: 32)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618
• Publications: 0 publications found

Genes affected

DAOA (HGNC:21191): (D-amino acid oxidase activator) This gene encodes a protein that may function as an activator of D-amino acid oxidase, which degrades the gliotransmitter D-serine, a potent activator of N-methyl-D-aspartate (NMDA) type glutamate receptors. Studies also suggest that one encoded isoform may play a role in mitochondrial function and dendritic arborization. Polymorphisms in this gene have been implicated in susceptibility to schizophrenia and bipolar affective disorder. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Mar 2011]

DAOA-AS1 (HGNC:30243): (DAOA antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5	c.281+6583C>A		intron_variant	Intron 4 of 5	ENST00000375936.9	NP_758958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAOA	ENST00000375936.9	c.281+6583C>A		intron_variant	Intron 4 of 5	1	NM_172370.5	ENSP00000365103.3
DAOA	ENST00000471432.3	n.*392+2058C>A		intron_variant	Intron 5 of 6	1		ENSP00000472857.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40044 AN: 151926 Hom.: 5447 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.253

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

GnomAD4 genome AF: 0.264 AC: 40071 AN: 152044 Hom.: 5453 Cov.: 32 AF XY: 0.262 AC XY: 19509 AN XY: 74326

African (AFR) AF: 0.221 AC: 9179 AN: 41472

American (AMR) AF: 0.262 AC: 4003 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3468

East Asian (EAS) AF: 0.143 AC: 739 AN: 5170

South Asian (SAS) AF: 0.220 AC: 1058 AN: 4820

European-Finnish (FIN) AF: 0.330 AC: 3487 AN: 10558

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19809 AN: 67974

Other (OTH) AF: 0.252 AC: 531 AN: 2110

Alfa AF: 0.274 Hom.: 7558

Bravo AF: 0.260

Asia WGS AF: 0.188 AC: 658 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.51
DANN	Benign	0.74
PhyloP100		-0.62
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9519688; hg19: chr13-106131617;