NM_172370.5:c.434A>G

Variant names:

• chr13-105490053-A-G
• rs367543081
• NM_172370.5:c.434A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_172370.5(DAOA):​c.434A>G​(p.Lys145Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000721 in 1,581,666 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: DAOA NM_172370.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.370
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011992693).

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.434A>G	p.Lys145Arg	missense	Exon 5 of 6	NP_758958.3
	DAOA	NM_001161812.1		c.350A>G	p.Lys117Arg	missense	Exon 4 of 5	NP_001155284.1	A2T115
	DAOA	NM_001384645.1		c.227A>G	p.Lys76Arg	missense	Exon 6 of 7	NP_001371574.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAOA	ENST00000375936.9	TSL:1 MANE Select	c.434A>G	p.Lys145Arg	missense	Exon 5 of 6	ENSP00000365103.3	P59103-1
	DAOA	ENST00000595812.2	TSL:1	c.350A>G	p.Lys117Arg	missense	Exon 4 of 5	ENSP00000469539.1	A2T115
	DAOA	ENST00000329625.9	TSL:1	c.221A>G	p.Lys74Arg	missense	Exon 4 of 4	ENSP00000329951.5	P59103-3

Frequencies

GnomAD3 genomes AF: 0.0000591 AC: 9 AN: 152170 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000122 AC: 23 AN: 188030 AF XY: 0.000129

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000360

Gnomad ASJ exome AF: 0.00223

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000129

Gnomad OTH exome AF: 0.000202

GnomAD4 exome AF: 0.0000735 AC: 105 AN: 1429378 Hom.: 0 Cov.: 32 AF XY: 0.0000720 AC XY: 51 AN XY: 708030

African (AFR) AF: 0.00 AC: 0 AN: 32630

American (AMR) AF: 0.0000509 AC: 2 AN: 39322

Ashkenazi Jewish (ASJ) AF: 0.00251 AC: 64 AN: 25484

East Asian (EAS) AF: 0.00 AC: 0 AN: 37980

South Asian (SAS) AF: 0.0000242 AC: 2 AN: 82804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51628

Middle Eastern (MID) AF: 0.000699 AC: 4 AN: 5726

European-Non Finnish (NFE) AF: 0.0000201 AC: 22 AN: 1094638

Other (OTH) AF: 0.000186 AC: 11 AN: 59166

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152288 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74466

African (AFR) AF: 0.00 AC: 0 AN: 41562

American (AMR) AF: 0.000131 AC: 2 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000215 Hom.: 0

Bravo AF: 0.000102

ExAC AF: 0.0000596 AC: 7

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.0043	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.37
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.068
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.98	D
Vest4		0.071
MVP		0.24
MPC		0.0056
ClinPred		0.064	T
GERP RS		1.4
Varity_R		0.19
gMVP		0.0065
Mutation Taster		=100/0	polymorphism

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: rs367543081; hg19: chr13-106142402;