rs367543078

Variant names:

• chr13-105467134-C-G
• rs367543078
• NM_172370.5:c.126C>G

Your query was ambiguous. Multiple possible variants found:

• chr13-105467134-C-G
• chr13-105467134-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172370.5(DAOA):​c.126C>G​(p.Asn42Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,455,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DAOA NM_172370.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.392
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19971451).

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.126C>G	p.Asn42Lys	missense	Exon 3 of 6	NP_758958.3
	DAOA	NM_001384644.1		c.126C>G	p.Asn42Lys	missense	Exon 2 of 6	NP_001371573.1	P59103-4
	DAOA	NM_001161812.1		c.-68C>G		5_prime_UTR	Exon 2 of 5	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.126C>G	p.Asn42Lys	missense	Exon 3 of 6	ENSP00000365103.3	P59103-1
	DAOA	ENST00000595812.2	TSL:1	c.-68C>G		5_prime_UTR	Exon 2 of 5	ENSP00000469539.1	A2T115
	DAOA	ENST00000329625.9	TSL:1	c.-88C>G		5_prime_UTR	Exon 2 of 4	ENSP00000329951.5	P59103-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000405 AC: 1 AN: 246794 AF XY: 0.00000746

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1455822 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 724320

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44472

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26014

East Asian (EAS) AF: 0.00 AC: 0 AN: 39462

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52712

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1108210

Other (OTH) AF: 0.00 AC: 0 AN: 60168

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.0000594

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	Uncertain	0.52
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.7
DANN	Benign	0.86
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.39
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.049
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.35
MutPred		0.16		Gain of ubiquitination at N42 (P = 0.0048)
MVP		0.30
MPC		0.0051
ClinPred		0.29	T
GERP RS		0.11
Varity_R		0.18
gMVP		0.041
Mutation Taster		=298/2	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: rs367543078; hg19: chr13-106119483;