Genetic Variant NM_001917.5:c.113G>T (chr12-108885119-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001917.5(DAO):c.113G>T(p.Arg38Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,034 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R38C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DAO
NM_001917.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.934

Publications

0 publications found

Variant links:

Genes affected

DAO (HGNC:2671): (D-amino acid oxidase) This gene encodes the peroxisomal enzyme D-amino acid oxidase. The enzyme is a flavoprotein which uses flavin adenine dinucleotide (FAD) as its prosthetic group. Its substrates include a wide variety of D-amino acids, but it is inactive on the naturally occurring L-amino acids. Its biological function is not known; it may act as a detoxifying agent which removes D-amino acids that accumulate during aging. In mice, it degrades D-serine, a co-agonist of the NMDA receptor. This gene may play a role in the pathophysiology of schizophrenia. [provided by RefSeq, Jul 2008]

DAO Gene-Disease associations (from GenCC):

amyotrophic lateral sclerosis
Inheritance: AD Classification: MODERATE, SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Ambry Genetics, Genomics England PanelApp, Orphanet, ClinGen

DAO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001917.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAO	NM_001917.5	MANE Select	c.113G>T	p.Arg38Leu	missense	Exon 2 of 11	NP_001908.3
DAO	NM_001413634.1		c.113G>T	p.Arg38Leu	missense	Exon 3 of 12	NP_001400563.1	P14920
DAO	NM_001413635.1		c.113G>T	p.Arg38Leu	missense	Exon 2 of 10	NP_001400564.1	A0A0S2Z3J4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DAO	ENST00000228476.8	TSL:1 MANE Select	c.113G>T	p.Arg38Leu	missense	Exon 2 of 11	ENSP00000228476.3	P14920
DAO	ENST00000551281.5	TSL:1	c.113G>T	p.Arg38Leu	missense	Exon 2 of 8	ENSP00000446853.1	A0A0B4J250
DAO	ENST00000547122.5	TSL:1	n.113G>T		non_coding_transcript_exon	Exon 2 of 10	ENSP00000448095.1	A0A0B4J257

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461034

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726606

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111316

Other (OTH)

AF:

0.00

AC:

AN:

60366

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.087

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.074

Eigen

Benign

0.013

Eigen_PC

Benign

0.093

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.072

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.36

MutationAssessor

Uncertain

2.7

PhyloP100

0.93

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.43

Sift

Benign

0.18

Sift4G

Benign

0.23

Polyphen

0.47

Vest4

0.59

MutPred

0.61

Loss of catalytic residue at R38 (P = 0.0482)

MVP

0.83

MPC

0.38

ClinPred

0.92

GERP RS

5.6

Varity_R

0.58

gMVP

0.77

Mutation Taster

=81/19

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over