chr12-108887351-C-T

Variant names:

• chr12-108887351-C-T
• rs75861794
• NM_001917.5:c.195-99C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.671

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]

ACMG classification

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	c.195-99C>T		intron_variant	Intron 2 of 10	ENST00000228476.8	NP_001908.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0696 AC: 10583 AN: 152016 Hom.: 888 Cov.: 32

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

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.: 32 AF XY: 0.0662 AC XY: 4924 AN XY: 74366

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.: 68

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

Submissions by phenotype

not provided Benign:2

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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

Other links and lift over

dbSNP: rs75861794; hg19: chr12-109281127;