ENST00000595812.2:c.-64A>G

Variant names:

• chr13-105467138-A-G
• rs1876580432
• ENST00000595812.2:c.-64A>G

Variant summary

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

The ENST00000595812.2(DAOA):​c.-64A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,453,902 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: DAOA ENST00000595812.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.265
• Publications: 0 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=0.081220895).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000595812.2. 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.130A>G	p.Ile44Val	missense	Exon 3 of 6	NP_758958.3
	DAOA	NM_001161812.1		c.-64A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001155284.1	A2T115
	DAOA	NM_001384645.1		c.-172A>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 7	NP_001371574.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAOA	ENST00000595812.2	TSL:1	c.-64A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000469539.1	A2T115
	DAOA	ENST00000329625.9	TSL:1	c.-84A>G		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000329951.5	P59103-3
	DAOA	ENST00000375936.9	TSL:1 MANE Select	c.130A>G	p.Ile44Val	missense	Exon 3 of 6	ENSP00000365103.3	P59103-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1453902 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 723346

African (AFR) AF: 0.0000300 AC: 1 AN: 33356

American (AMR) AF: 0.0000226 AC: 1 AN: 44210

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39446

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85200

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1107300

Other (OTH) AF: 0.00 AC: 0 AN: 60112

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.5
DANN	Benign	0.78
DEOGEN2	Benign	0.0012	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.026	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0051	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.27
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.029
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.97	T
Polyphen		0.85	P
Vest4		0.14
MutPred		0.20		Loss of stability (P = 0.1196)
MVP		0.095
MPC		0.0034
ClinPred		0.19	T
GERP RS		0.98
Varity_R		0.077
gMVP		0.0063
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1876580432; hg19: chr13-106119487;