dbSNP rs72549478: DAOA:p.His16Pro (chr13-105472644-A-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001161812.1(DAOA):c.47A>C(p.His16Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H16L) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

DAOA
NM_001161812.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.263

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04961741).

BP6

Variant 13-105472644-A-C is Benign according to our data. Variant chr13-105472644-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3080049.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAOA	NM_172370.5	MANE Select	c.240A>C	p.Ser80Ser	synonymous	Exon 4 of 6	NP_758958.3
DAOA	NM_001161812.1		c.47A>C	p.His16Pro	missense	Exon 3 of 5	NP_001155284.1	A2T115
DAOA	NM_001384644.1		c.240A>C	p.Ser80Ser	synonymous	Exon 3 of 6	NP_001371573.1	P59103-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAOA	ENST00000595812.2	TSL:1	c.47A>C	p.His16Pro	missense	Exon 3 of 5	ENSP00000469539.1	A2T115
DAOA	ENST00000375936.9	TSL:1 MANE Select	c.240A>C	p.Ser80Ser	synonymous	Exon 4 of 6	ENSP00000365103.3	P59103-1
DAOA	ENST00000329625.9	TSL:1	c.27A>C	p.Ser9Ser	synonymous	Exon 3 of 4	ENSP00000329951.5	P59103-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249382

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000827

AC:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.38

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.10

FATHMM_MKL

Benign

0.0098

LIST_S2

Benign

0.19

MetaRNN

Benign

0.050

PhyloP100

-0.26

PrimateAI

Benign

0.25

Sift4G

Benign

0.20

Polyphen

0.038

GERP RS

0.41

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over