13-105468070-A-G

Variant names:

• chr13-105468070-A-G
• rs3918341
• NM_172370.5:c.133+929A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_172370.5(DAOA):​c.133+929A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 151,820 control chromosomes in the GnomAD database, including 10,837 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 0.35 (10837 hom., cov: 31)
• Consequence: DAOA NM_172370.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.408
• Publications: 6 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5	c.133+929A>G		intron_variant	Intron 3 of 5	ENST00000375936.9	NP_758958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAOA	ENST00000375936.9	c.133+929A>G		intron_variant	Intron 3 of 5	1	NM_172370.5	ENSP00000365103.3
DAOA	ENST00000471432.3	n.*54+348A>G		intron_variant	Intron 2 of 6	1		ENSP00000472857.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52814 AN: 151702 Hom.: 10834 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.624

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.415

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.348 AC: 52828 AN: 151820 Hom.: 10837 Cov.: 31 AF XY: 0.355 AC XY: 26350 AN XY: 74160

African (AFR) AF: 0.128 AC: 5313 AN: 41432

American (AMR) AF: 0.431 AC: 6577 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1411 AN: 3468

East Asian (EAS) AF: 0.625 AC: 3199 AN: 5120

South Asian (SAS) AF: 0.445 AC: 2136 AN: 4800

European-Finnish (FIN) AF: 0.450 AC: 4726 AN: 10508

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.415 AC: 28198 AN: 67928

Other (OTH) AF: 0.362 AC: 763 AN: 2110

Alfa AF: 0.383 Hom.: 2117

Bravo AF: 0.335

Asia WGS AF: 0.481 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.2
DANN	Benign	0.61
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3918341; hg19: chr13-106120419;