rs3916968

Variant names:

• chr13-105475180-C-T
• rs3916968
• NM_172370.5:c.281+2495C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_172370.5(DAOA):​c.281+2495C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 301,528 control chromosomes in the GnomAD database, including 14,675 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 (7178 hom., cov: 32)
  • Exomes 𝑓: 0.32 (7497 hom.)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.717
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.321 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+2495C>T		intron	N/A	NP_758958.3
	DAOA	NM_001384644.1		c.375+110C>T		intron	N/A	NP_001371573.1	P59103-4
	DAOA	NM_001161812.1		c.88+2495C>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+2495C>T		intron	N/A	ENSP00000365103.3	P59103-1
	DAOA	ENST00000595812.2	TSL:1	c.88+2495C>T		intron	N/A	ENSP00000469539.1	A2T115
	DAOA	ENST00000329625.9	TSL:1	c.68+2495C>T		intron	N/A	ENSP00000329951.5	P59103-3

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46640 AN: 151892 Hom.: 7174 Cov.: 32

Gnomad AFR AF: 0.326

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.324

GnomAD4 exome AF: 0.317 AC: 47400 AN: 149516 Hom.: 7497 AF XY: 0.321 AC XY: 23090 AN XY: 71988

African (AFR) AF: 0.342 AC: 905 AN: 2646

American (AMR) AF: 0.247 AC: 43 AN: 174

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 300 AN: 910

East Asian (EAS) AF: 0.236 AC: 147 AN: 622

South Asian (SAS) AF: 0.326 AC: 955 AN: 2932

European-Finnish (FIN) AF: 0.250 AC: 36 AN: 144

Middle Eastern (MID) AF: 0.356 AC: 101 AN: 284

European-Non Finnish (NFE) AF: 0.317 AC: 43349 AN: 136946

Other (OTH) AF: 0.322 AC: 1564 AN: 4858

GnomAD4 genome AF: 0.307 AC: 46654 AN: 152012 Hom.: 7178 Cov.: 32 AF XY: 0.304 AC XY: 22588 AN XY: 74286

African (AFR) AF: 0.326 AC: 13529 AN: 41492

American (AMR) AF: 0.290 AC: 4434 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1093 AN: 3464

East Asian (EAS) AF: 0.223 AC: 1147 AN: 5150

South Asian (SAS) AF: 0.311 AC: 1500 AN: 4818

European-Finnish (FIN) AF: 0.247 AC: 2606 AN: 10566

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21231 AN: 67916

Other (OTH) AF: 0.323 AC: 682 AN: 2112

Alfa AF: 0.311 Hom.: 4907

Bravo AF: 0.310

Asia WGS AF: 0.280 AC: 974 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	14
DANN	Benign	0.73
PhyloP100		0.72
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3916968;

hg19: chr13-106127529;