Genetic Variant NM_172370.5:c.406C>G (chr13-105490025-C-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_172370.5(DAOA):c.406C>G(p.Gln136Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000682 in 1,608,548 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00037 ( 7 hom. )

Consequence

DAOA
NM_172370.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.699

Publications

1 publications found

Variant links:

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 links:

DAOA-AS1 (HGNC:30243): (DAOA antisense RNA 1)

DAOA-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004847318).

BP6

Variant 13-105490025-C-G is Benign according to our data. Variant chr13-105490025-C-G is described in ClinVar as Benign. ClinVar VariationId is 768629.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_172370.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAOA	NM_172370.5	MANE Select	c.406C>G	p.Gln136Glu	missense	Exon 5 of 6	NP_758958.3
DAOA	NM_001161812.1		c.322C>G	p.Gln108Glu	missense	Exon 4 of 5	NP_001155284.1	A2T115
DAOA	NM_001384645.1		c.199C>G	p.Gln67Glu	missense	Exon 6 of 7	NP_001371574.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAOA	ENST00000375936.9	TSL:1 MANE Select	c.406C>G	p.Gln136Glu	missense	Exon 5 of 6	ENSP00000365103.3	P59103-1
DAOA	ENST00000595812.2	TSL:1	c.322C>G	p.Gln108Glu	missense	Exon 4 of 5	ENSP00000469539.1	A2T115
DAOA	ENST00000329625.9	TSL:1	c.193C>G	p.Gln65Glu	missense	Exon 4 of 4	ENSP00000329951.5	P59103-3

Frequencies

GnomAD3 genomes

AF:

0.00372

AC:

565

AN:

152034

Hom.:

Cov.:

show subpopulations

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:

0.000984

AC:

229

AN:

232748

AF XY:

0.000805

show subpopulations

Gnomad AFR exome

AF:

0.0140

Gnomad AMR exome

AF:

0.000790

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000974

Gnomad OTH exome

AF:

0.000348

GnomAD4 exome

AF:

0.000365

AC:

532

AN:

1456396

Hom.:

Cov.:

AF XY:

0.000327

AC XY:

237

AN XY:

724078

show subpopulations

African (AFR)

AF:

0.0138

AC:

459

AN:

33352

American (AMR)

AF:

0.000846

AC:

AN:

43732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25996

East Asian (EAS)

AF:

0.00

AC:

AN:

39396

South Asian (SAS)

AF:

0.00

AC:

AN:

85594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1109272

Other (OTH)

AF:

0.000498

AC:

AN:

60192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00371

AC:

565

AN:

152152

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

247

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0126

AC:

522

AN:

41502

American (AMR)

AF:

0.00229

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68004

Other (OTH)

AF:

0.00284

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

114

142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000526

Hom.:

Bravo

AF:

0.00417

ESP6500AA

AF:

0.0121

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00108

AC:

130

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.32

(source)

DANN

Benign

0.39

DEOGEN2

Benign

0.0050

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.70

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.3

REVEL

Benign

0.030

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0040

Vest4

0.19

MVP

0.10

MPC

0.0029

ClinPred

0.010

GERP RS

-1.6

Varity_R

0.17

gMVP

0.0017

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over