chr13-105467118-C-A

Variant names:

• chr13-105467118-C-A
• ENST00000595812.2:c.-84C>A

Variant summary

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

The NM_001161812.1(DAOA):​c.-84C>A 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 1,457,782 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 NM_001161812.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.64
• 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=0.11047202).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161812.1. 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.110C>A	p.Ser37Tyr	missense	Exon 3 of 6	NP_758958.3
	DAOA	NM_001161812.1		c.-84C>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_001155284.1	A2T115
	DAOA	NM_001384645.1		c.-192C>A		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.-84C>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000469539.1	A2T115
	DAOA	ENST00000329625.9	TSL:1	c.-104C>A		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	ENSP00000329951.5	P59103-3
	DAOA	ENST00000375936.9	TSL:1 MANE Select	c.110C>A	p.Ser37Tyr	missense	Exon 3 of 6	ENSP00000365103.3	P59103-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1457782 Hom.: 0 Cov.: 30 AF XY: 0.00000414 AC XY: 3 AN XY: 725274

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000299 AC: 1 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39478

South Asian (SAS) AF: 0.00 AC: 0 AN: 85922

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109410

Other (OTH) AF: 0.0000166 AC: 1 AN: 60262

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000416442), which strongly suggests a high chance of mosaicism in these individuals.

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	Uncertain	0.50
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.0
DANN	Benign	0.82
DEOGEN2	Benign	0.027	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.85
FATHMM_MKL	Benign	0.0081	N
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.6
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.095
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.012	D
Polyphen		0.98	D
Vest4		0.18
MutPred		0.21		Loss of sheet (P = 0.0126)
MVP		0.16
MPC		0.0059
ClinPred		0.30	T
GERP RS		-1.6
Varity_R		0.095
gMVP		0.023
Mutation Taster		=300/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr13-106119467;