NM_172370.5:c.282-5518T>A

Variant names:

• chr13-105484383-T-A
• rs7139958
• NM_172370.5:c.282-5518T>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.282-5518T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 151,972 control chromosomes in the GnomAD database, including 10,094 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 0.33 (10094 hom., cov: 33)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.578 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5	c.282-5518T>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.282-5518T>A		intron_variant	Intron 4 of 5	1	NM_172370.5	ENSP00000365103.3
DAOA	ENST00000471432.3	n.*393-5409T>A		intron_variant	Intron 5 of 6	1		ENSP00000472857.1

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50585 AN: 151854 Hom.: 10092 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.595

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.367

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

GnomAD4 genome AF: 0.333 AC: 50593 AN: 151972 Hom.: 10094 Cov.: 33 AF XY: 0.342 AC XY: 25424 AN XY: 74276

African (AFR) AF: 0.111 AC: 4620 AN: 41540

American (AMR) AF: 0.417 AC: 6363 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1444 AN: 3464

East Asian (EAS) AF: 0.595 AC: 3070 AN: 5158

South Asian (SAS) AF: 0.541 AC: 2612 AN: 4826

European-Finnish (FIN) AF: 0.403 AC: 4234 AN: 10512

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27032 AN: 67886

Other (OTH) AF: 0.365 AC: 771 AN: 2112

Alfa AF: 0.367 Hom.: 1439

Bravo AF: 0.318

Asia WGS AF: 0.507 AC: 1755 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.2
DANN	Benign	0.87
PhyloP100		1.7
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: rs7139958; hg19: chr13-106136732;