Genetic Variant NM_001917.5:c.195-99C>T (chr12-108887351-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001917.5(DAO):c.195-99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 875,270 control chromosomes in the GnomAD database, including 1,481 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.070 ( 891 hom., cov: 32)

Exomes 𝑓: 0.023 ( 590 hom. )

Consequence

DAO
NM_001917.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.671

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-108887351-C-T is Benign according to our data. Variant chr12-108887351-C-T is described in ClinVar as [Benign]. Clinvar id is 1287855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAO	NM_001917.5 link	c.195-99C>T		intron_variant	Intron 2 of 10	ENST00000228476.8	NP_001908.3	P14920A0A024RBI1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000228476.8 link	c.195-99C>T		intron_variant	Intron 2 of 10	1	NM_001917.5	ENSP00000228476.3		P14920

Frequencies

GnomAD3 genomes

AF:

0.0696

AC:

10583

AN:

152016

Hom.:

888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0310

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0189

Gnomad FIN

AF:

0.0139

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0536

GnomAD4 exome

AF:

0.0229

AC:

16540

AN:

723136

Hom.:

590

AF XY:

0.0217

AC XY:

8421

AN XY:

387444

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.0209

Gnomad4 ASJ exome

AF:

0.0226

Gnomad4 EAS exome

AF:

0.0000824

Gnomad4 SAS exome

AF:

0.0190

Gnomad4 FIN exome

AF:

0.0130

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0315

GnomAD4 genome

AF:

0.0697

AC:

10598

AN:

152134

Hom.:

891

Cov.:

AF XY:

0.0662

AC XY:

4924

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.204

Gnomad4 AMR

AF:

0.0309

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0189

Gnomad4 FIN

AF:

0.0139

Gnomad4 NFE

AF:

0.0176

Gnomad4 OTH

AF:

0.0573

Alfa

AF:

0.0355

Hom.:

Bravo

AF:

0.0775

Asia WGS

AF:

0.0480

AC:

167

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 19, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

4.1

DANN

Benign

0.72

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over