13-105487313-T-G

Variant names:

• chr13-105487313-T-G
• rs947267
• NM_172370.5:c.282-2588T>G

Variant summary

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

The NM_172370.5(DAOA):​c.282-2588T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,922 control chromosomes in the GnomAD database, including 20,147 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 0.50 (20147 hom., cov: 32)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.61
• Publications: 29 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5	c.282-2588T>G		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.282-2588T>G		intron_variant	Intron 4 of 5	1	NM_172370.5	ENSP00000365103.3
DAOA	ENST00000471432.3	n.*393-2479T>G		intron_variant	Intron 5 of 6	1		ENSP00000472857.1

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75818 AN: 151804 Hom.: 20119 Cov.: 32

Gnomad AFR AF: 0.685

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.437

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.463

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.429

Gnomad OTH AF: 0.475

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

GnomAD4 genome AF: 0.500 AC: 75899 AN: 151922 Hom.: 20147 Cov.: 32 AF XY: 0.495 AC XY: 36720 AN XY: 74252

African (AFR) AF: 0.685 AC: 28376 AN: 41408

American (AMR) AF: 0.437 AC: 6673 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1518 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1907 AN: 5142

South Asian (SAS) AF: 0.382 AC: 1839 AN: 4814

European-Finnish (FIN) AF: 0.463 AC: 4891 AN: 10562

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.429 AC: 29172 AN: 67942

Other (OTH) AF: 0.475 AC: 1001 AN: 2108

Alfa AF: 0.464 Hom.: 29279

Bravo AF: 0.509

Asia WGS AF: 0.410 AC: 1427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.019
DANN	Benign	0.78
PhyloP100		-3.6
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: rs947267; hg19: chr13-106139662;