chr13-105473959-C-T

Variant names:

• chr13-105473959-C-T
• rs9301030
• NM_172370.5:c.281+1274C>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+1274C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,852 control chromosomes in the GnomAD database, including 7,563 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 0.31 (7563 hom., cov: 31)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172370.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAOA	NM_172370.5	MANE Select	c.281+1274C>T		intron	N/A	NP_758958.3
	DAOA	NM_001384644.1		c.282-1018C>T		intron	N/A	NP_001371573.1	P59103-4
	DAOA	NM_001161812.1		c.88+1274C>T		intron	N/A	NP_001155284.1	A2T115

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAOA	ENST00000375936.9	TSL:1 MANE Select	c.281+1274C>T		intron	N/A	ENSP00000365103.3	P59103-1
	DAOA	ENST00000595812.2	TSL:1	c.88+1274C>T		intron	N/A	ENSP00000469539.1	A2T115
	DAOA	ENST00000329625.9	TSL:1	c.68+1274C>T		intron	N/A	ENSP00000329951.5	P59103-3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47438 AN: 151734 Hom.: 7552 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.406

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.313 AC: 47477 AN: 151852 Hom.: 7563 Cov.: 31 AF XY: 0.310 AC XY: 23013 AN XY: 74208

African (AFR) AF: 0.273 AC: 11332 AN: 41440

American (AMR) AF: 0.296 AC: 4524 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3468

East Asian (EAS) AF: 0.203 AC: 1050 AN: 5160

South Asian (SAS) AF: 0.282 AC: 1359 AN: 4818

European-Finnish (FIN) AF: 0.364 AC: 3837 AN: 10544

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23154 AN: 67846

Other (OTH) AF: 0.302 AC: 637 AN: 2108

Alfa AF: 0.329 Hom.: 19577

Bravo AF: 0.310

Asia WGS AF: 0.255 AC: 888 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.53
PhyloP100		-0.75
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: rs9301030; hg19: chr13-106126308;