13-105489886-C-T

Variant names:

• chr13-105489886-C-T
• rs778294
• ENST00000595812.2:c.183C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000595812.2(DAOA):​c.183C>T​(p.Thr61Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.281 in 1,613,382 control chromosomes in the GnomAD database, including 65,280 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 0.26 (5265 hom., cov: 31)
  • Exomes 𝑓: 0.28 (60015 hom.)
• Consequence: DAOA ENST00000595812.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.22
• Publications: 47 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BP7: Synonymous conserved (PhyloP=-2.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5	c.282-15C>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	ENST00000471432.3	n.*487C>T		non_coding_transcript_exon_variant	Exon 6 of 7	1		ENSP00000472857.1
DAOA	ENST00000471432.3	n.*487C>T		3_prime_UTR_variant	Exon 6 of 7	1		ENSP00000472857.1
DAOA	ENST00000375936.9	c.282-15C>T		intron_variant	Intron 4 of 5	1	NM_172370.5	ENSP00000365103.3

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39396 AN: 151742 Hom.: 5259 Cov.: 31

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.249

GnomAD2 exomes AF: 0.266 AC: 65632 AN: 246952 AF XY: 0.261

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.134

Gnomad FIN exome AF: 0.291

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.283 AC: 413162 AN: 1461522 Hom.: 60015 Cov.: 36 AF XY: 0.280 AC XY: 203438 AN XY: 727052

African (AFR) AF: 0.216 AC: 7225 AN: 33462

American (AMR) AF: 0.320 AC: 14283 AN: 44686

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 6810 AN: 26128

East Asian (EAS) AF: 0.144 AC: 5711 AN: 39686

South Asian (SAS) AF: 0.207 AC: 17840 AN: 86246

European-Finnish (FIN) AF: 0.292 AC: 15603 AN: 53400

Middle Eastern (MID) AF: 0.198 AC: 1138 AN: 5760

European-Non Finnish (NFE) AF: 0.296 AC: 328602 AN: 1111780

Other (OTH) AF: 0.264 AC: 15950 AN: 60374

GnomAD4 genome AF: 0.260 AC: 39419 AN: 151860 Hom.: 5265 Cov.: 31 AF XY: 0.257 AC XY: 19076 AN XY: 74204

African (AFR) AF: 0.217 AC: 8979 AN: 41424

American (AMR) AF: 0.266 AC: 4051 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 888 AN: 3470

East Asian (EAS) AF: 0.135 AC: 694 AN: 5142

South Asian (SAS) AF: 0.212 AC: 1019 AN: 4796

European-Finnish (FIN) AF: 0.303 AC: 3195 AN: 10536

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.290 AC: 19694 AN: 67938

Other (OTH) AF: 0.248 AC: 521 AN: 2104

Alfa AF: 0.278 Hom.: 20547

Bravo AF: 0.259

Asia WGS AF: 0.177 AC: 619 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.27
DANN	Benign	0.51
PhyloP100		-2.2
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: rs778294; hg19: chr13-106142235; COSMIC: COSV61602599;