chr13-105467143-T-A

Variant names:

• chr13-105467143-T-A
• rs148297571
• NM_172370.5:c.133+2T>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_172370.5(DAOA):​c.133+2T>A variant causes a splice donor, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,602,422 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0073 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00075 (16 hom.)
• Consequence: DAOA NM_172370.5 splice_donor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.915
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 13-105467143-T-A is Benign according to our data. Variant chr13-105467143-T-A is described in ClinVar as Benign. ClinVar VariationId is 3777967.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0073 (1112/152320) while in subpopulation AFR AF = 0.0256 (1064/41572). AF 95% confidence interval is 0.0243. There are 9 homozygotes in GnomAd4. There are 551 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

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.133+2T>A		splice_donor intron	N/A	NP_758958.3
	DAOA	NM_001384644.1		c.133+2T>A		splice_donor intron	N/A	NP_001371573.1	P59103-4
	DAOA	NM_001161812.1		c.-61+2T>A		splice_donor intron	N/A	NP_001155284.1	A2T115

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAOA	ENST00000375936.9	TSL:1 MANE Select	c.133+2T>A		splice_donor intron	N/A	ENSP00000365103.3	P59103-1
	DAOA	ENST00000595812.2	TSL:1	c.-61+2T>A		splice_donor intron	N/A	ENSP00000469539.1	A2T115
	DAOA	ENST00000329625.9	TSL:1	c.-81+2T>A		splice_donor intron	N/A	ENSP00000329951.5	P59103-3

Frequencies

GnomAD3 genomes AF: 0.00731 AC: 1113 AN: 152202 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00382

GnomAD2 exomes AF: 0.00181 AC: 440 AN: 242590 AF XY: 0.00139

Gnomad AFR exome AF: 0.0259

Gnomad AMR exome AF: 0.00103

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000898

Gnomad OTH exome AF: 0.00103

GnomAD4 exome AF: 0.000752 AC: 1090 AN: 1450102 Hom.: 16 Cov.: 30 AF XY: 0.000638 AC XY: 460 AN XY: 721238

African (AFR) AF: 0.0280 AC: 931 AN: 33250

American (AMR) AF: 0.00110 AC: 48 AN: 43574

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25824

East Asian (EAS) AF: 0.00 AC: 0 AN: 39408

South Asian (SAS) AF: 0.0000475 AC: 4 AN: 84288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52464

Middle Eastern (MID) AF: 0.00106 AC: 6 AN: 5686

European-Non Finnish (NFE) AF: 0.0000136 AC: 15 AN: 1105672

Other (OTH) AF: 0.00143 AC: 86 AN: 59936

GnomAD4 genome AF: 0.00730 AC: 1112 AN: 152320 Hom.: 9 Cov.: 32 AF XY: 0.00740 AC XY: 551 AN XY: 74486

African (AFR) AF: 0.0256 AC: 1064 AN: 41572

American (AMR) AF: 0.00216 AC: 33 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68030

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00123 Hom.: 0

Bravo AF: 0.00845

ESP6500AA AF: 0.0254 AC: 91

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00223 AC: 269

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.77	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	18
DANN	Benign	0.62
Eigen	Benign	0.10
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.022	N
PhyloP100		0.92
GERP RS		0.61
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Benign	0.67
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.97		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs148297571; hg19: chr13-106119492;