13-105472644-A-T

Variant names:

• chr13-105472644-A-T
• rs72549478
• ENST00000595812.2:c.47A>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001161812.1(DAOA):​c.47A>T​(p.His16Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000683 in 1,614,082 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H16P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (7 hom.)
• Consequence: DAOA NM_001161812.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.263
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0045135617).
• BP6: Variant 13-105472644-A-T is Benign according to our data. Variant chr13-105472644-A-T is described in ClinVar as Benign. ClinVar VariationId is 768627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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.240A>T	p.Ser80Ser	synonymous	Exon 4 of 6	NP_758958.3
	DAOA	NM_001161812.1		c.47A>T	p.His16Leu	missense	Exon 3 of 5	NP_001155284.1	A2T115
	DAOA	NM_001384644.1		c.240A>T	p.Ser80Ser	synonymous	Exon 3 of 6	NP_001371573.1	P59103-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAOA	ENST00000595812.2	TSL:1	c.47A>T	p.His16Leu	missense	Exon 3 of 5	ENSP00000469539.1	A2T115
	DAOA	ENST00000375936.9	TSL:1 MANE Select	c.240A>T	p.Ser80Ser	synonymous	Exon 4 of 6	ENSP00000365103.3	P59103-1
	DAOA	ENST00000329625.9	TSL:1	c.27A>T	p.Ser9Ser	synonymous	Exon 3 of 4	ENSP00000329951.5	P59103-3

Frequencies

GnomAD3 genomes AF: 0.00371 AC: 565 AN: 152192 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.0126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00229

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.000954 AC: 238 AN: 249382 AF XY: 0.000769

Gnomad AFR exome AF: 0.0135

Gnomad AMR exome AF: 0.000753

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000368 AC: 538 AN: 1461772 Hom.: 7 Cov.: 31 AF XY: 0.000329 AC XY: 239 AN XY: 727180

African (AFR) AF: 0.0139 AC: 465 AN: 33480

American (AMR) AF: 0.000827 AC: 37 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1111920

Other (OTH) AF: 0.000497 AC: 30 AN: 60394

GnomAD4 genome AF: 0.00371 AC: 565 AN: 152310 Hom.: 3 Cov.: 32 AF XY: 0.00330 AC XY: 246 AN XY: 74488

African (AFR) AF: 0.0126 AC: 522 AN: 41568

American (AMR) AF: 0.00229 AC: 35 AN: 15296

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68020

Other (OTH) AF: 0.00284 AC: 6 AN: 2116

Alfa AF: 0.000104 Hom.: 0

Bravo AF: 0.00418

ESP6500AA AF: 0.0121 AC: 46

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00108 AC: 130

ClinVar

ClinVar submissions as Germline

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
AlphaMissense	Benign	0.29
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.36
DANN	Benign	0.49
DEOGEN2	Benign	0.10	T
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.20	T
MetaRNN	Benign	0.0045	T
PhyloP100		-0.26
PrimateAI	Benign	0.25	T
Sift4G	Benign	0.37	T
Polyphen		0.0010	B
GERP RS		0.41
Mutation Taster		=100/0	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

dbSNP: rs72549478; hg19: chr13-106124993;