Genetic Variant NM_172370.5:c.271C>A (chr13-105472675-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_172370.5(DAOA):c.271C>A(p.Pro91Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,460,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P91S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DAOA
NM_172370.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.664

Publications

0 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: 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=0.15663162).

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.271C>A	p.Pro91Thr	missense	Exon 4 of 6	NP_758958.3
DAOA	NM_001384644.1		c.271C>A	p.Pro91Thr	missense	Exon 3 of 6	NP_001371573.1	P59103-4
DAOA	NM_001161812.1		c.78C>A	p.Ser26Arg	missense	Exon 3 of 5	NP_001155284.1	A2T115

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAOA	ENST00000375936.9	TSL:1 MANE Select	c.271C>A	p.Pro91Thr	missense	Exon 4 of 6	ENSP00000365103.3	P59103-1
DAOA	ENST00000595812.2	TSL:1	c.78C>A	p.Ser26Arg	missense	Exon 3 of 5	ENSP00000469539.1	A2T115
DAOA	ENST00000329625.9	TSL:1	c.58C>A	p.Pro20Thr	missense	Exon 3 of 4	ENSP00000329951.5	P59103-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1460554

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726584

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33438

American (AMR)

AF:

0.00

AC:

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26064

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

85980

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111402

Other (OTH)

AF:

0.00

AC:

AN:

60340

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.032

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.45

M_CAP

Benign

0.0046

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.66

PROVEAN

Pathogenic

-6.9

REVEL

Benign

0.055

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.99

Vest4

0.095

MutPred

0.35

Gain of helix (P = 0.0093)

MVP

0.25

MPC

0.0068

ClinPred

0.40

GERP RS

0.15

Varity_R

0.41

gMVP

0.017

Mutation Taster

=99/1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over