13-105472657-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172370.5(DAOA):c.253G>T(p.Val85Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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)
• Consequence: DAOA NM_172370.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.82

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10387543).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAOA	NM_172370.5	c.253G>T	p.Val85Phe	missense_variant	4/6	ENST00000375936.9
DAOA-AS1	NR_040247.1	n.506-6237C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAOA	ENST00000375936.9	c.253G>T	p.Val85Phe	missense_variant	4/6	1	NM_172370.5	P2
DAOA-AS1	ENST00000448407.1	n.506-6237C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Psychiatry Genetics Yale University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	0.23
Dann	Benign	0.42
DEOGEN2	Benign	0.038	T;.;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0060	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N;.;N
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Uncertain	-3.6	D;D;.
REVEL	Benign	0.076
Sift	Benign	0.032	D;T;.
Sift4G	Pathogenic	0.0	D;T;D
Polyphen		0.76	P;.;P
Vest4		0.39
MutPred		0.32		Gain of catalytic residue at W84 (P = 4e-04);.;Gain of catalytic residue at W84 (P = 4e-04);
MVP		0.061
MPC		0.0034
ClinPred		0.35	T
GERP RS		-4.8
Varity_R		0.16
gMVP		0.017

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

Publications

LitVar

Other links and lift over

dbSNP: rs367543079; hg19: chr13-106125006;