13-105472675-C-A

Variant names:

• chr13-105472675-C-A
• NM_172370.5:c.271C>A

Variant summary

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

The NM_172370.5(DAOA):​c.271C>A​(p.Pro91Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DAOA NM_172370.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.664

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=0.15663162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAOA	NM_172370.5	c.271C>A	p.Pro91Thr	missense_variant	Exon 4 of 6	ENST00000375936.9	NP_758958.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAOA	ENST00000375936.9	c.271C>A	p.Pro91Thr	missense_variant	Exon 4 of 6	1	NM_172370.5	ENSP00000365103.3
DAOA	ENST00000471432.3	n.*192C>A		non_coding_transcript_exon_variant	Exon 3 of 7	1		ENSP00000472857.1
DAOA	ENST00000471432.3	n.*192C>A		3_prime_UTR_variant	Exon 3 of 7	1		ENSP00000472857.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1460554 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726584

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	12
DANN	Benign	0.97
DEOGEN2	Benign	0.032	T;.;T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.45	.;T;T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.16	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;.;N
PROVEAN	Pathogenic	-6.9	D;D;.
REVEL	Benign	0.055
Sift	Pathogenic	0.0	D;D;.
Sift4G	Pathogenic	0.0	D;D;D
Polyphen		0.99	D;.;D
Vest4		0.095
MutPred		0.35		Gain of helix (P = 0.0093);.;Gain of helix (P = 0.0093);
MVP		0.25
MPC		0.0068
ClinPred		0.40	T
GERP RS		0.15
Varity_R		0.41
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-106125024;