13-105478789-C-T

Variant names:

• chr13-105478789-C-T
• rs2153674
• NM_172370.5:c.281+6104C>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.281+6104C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,958 control chromosomes in the GnomAD database, including 25,115 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 0.57 (25115 hom., cov: 33)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5	c.281+6104C>T		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+6104C>T		intron_variant	Intron 4 of 5	1	NM_172370.5	ENSP00000365103.3
DAOA	ENST00000471432.3	n.*392+1579C>T		intron_variant	Intron 5 of 6	1		ENSP00000472857.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86740 AN: 151842 Hom.: 25100 Cov.: 33

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.604

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.537

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.537

Gnomad OTH AF: 0.593

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

GnomAD4 genome AF: 0.571 AC: 86798 AN: 151958 Hom.: 25115 Cov.: 33 AF XY: 0.577 AC XY: 42870 AN XY: 74302

African (AFR) AF: 0.576 AC: 23886 AN: 41456

American (AMR) AF: 0.592 AC: 9052 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 2095 AN: 3466

East Asian (EAS) AF: 0.855 AC: 4420 AN: 5168

South Asian (SAS) AF: 0.706 AC: 3403 AN: 4820

European-Finnish (FIN) AF: 0.537 AC: 5654 AN: 10530

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.537 AC: 36449 AN: 67926

Other (OTH) AF: 0.593 AC: 1252 AN: 2110

Alfa AF: 0.530 Hom.: 9538

Bravo AF: 0.569

Asia WGS AF: 0.754 AC: 2621 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.49
DANN	Benign	0.39
PhyloP100		-0.093
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: rs2153674; hg19: chr13-106131138;