13-105468636-G-T

Variant names:

• chr13-105468636-G-T
• rs12874006
• NM_172370.5:c.133+1495G>T

Variant summary

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

The NM_172370.5(DAOA):​c.133+1495G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,206 control chromosomes in the GnomAD database, including 1,141 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 0.12 (1141 hom., cov: 33)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5	c.133+1495G>T		intron_variant	Intron 3 of 5	ENST00000375936.9	NP_758958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAOA	ENST00000375936.9	c.133+1495G>T		intron_variant	Intron 3 of 5	1	NM_172370.5	ENSP00000365103.3
DAOA	ENST00000471432.3	n.*54+914G>T		intron_variant	Intron 2 of 6	1		ENSP00000472857.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17779 AN: 152088 Hom.: 1141 Cov.: 33

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0661

Gnomad FIN AF: 0.0833

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.124

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

GnomAD4 genome AF: 0.117 AC: 17781 AN: 152206 Hom.: 1141 Cov.: 33 AF XY: 0.113 AC XY: 8382 AN XY: 74394

African (AFR) AF: 0.141 AC: 5846 AN: 41522

American (AMR) AF: 0.115 AC: 1759 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 319 AN: 3472

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0662 AC: 319 AN: 4822

European-Finnish (FIN) AF: 0.0833 AC: 881 AN: 10578

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.122 AC: 8311 AN: 68016

Other (OTH) AF: 0.123 AC: 261 AN: 2116

Alfa AF: 0.112 Hom.: 633

Bravo AF: 0.121

Asia WGS AF: 0.0450 AC: 156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.0
DANN	Benign	0.58
PhyloP100		-0.22
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: rs12874006; hg19: chr13-106120985;