NM_172370.5:c.253G>T

Variant names:

• chr13-105472657-G-T
• rs367543079
• NM_172370.5:c.253G>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.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. 14/21 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)
• Consequence: DAOA NM_172370.5 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -1.82
• 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=0.10387543).

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.253G>T	p.Val85Phe	missense	Exon 4 of 6	NP_758958.3
	DAOA	NM_001384644.1		c.253G>T	p.Val85Phe	missense	Exon 3 of 6	NP_001371573.1	P59103-4
	DAOA	NM_001161814.1		c.40G>T	p.Val14Phe	missense	Exon 4 of 6	NP_001155286.1	P59103-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAOA	ENST00000375936.9	TSL:1 MANE Select	c.253G>T	p.Val85Phe	missense	Exon 4 of 6	ENSP00000365103.3	P59103-1
	DAOA	ENST00000329625.9	TSL:1	c.40G>T	p.Val14Phe	missense	Exon 3 of 4	ENSP00000329951.5	P59103-3
	DAOA	ENST00000595812.2	TSL:1	c.60G>T	p.Gly20Gly	synonymous	Exon 3 of 5	ENSP00000469539.1	A2T115

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

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	0.32
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.23
DANN	Benign	0.42
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.8
PROVEAN	Uncertain	-3.6	D
REVEL	Benign	0.076
Sift	Benign	0.032	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.76	P
Vest4		0.39
MutPred		0.32		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
Mutation Taster		=99/1	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: rs367543079; hg19: chr13-106125006;