rs3918347

Variant names:

• chr12-108899544-A-G
• rs3918347
• NM_001917.5:c.912+69A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001917.5(DAO):​c.912+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 1,331,902 control chromosomes in the GnomAD database, including 66,870 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (9689 hom., cov: 32)
  • Exomes 𝑓: 0.30 (57181 hom.)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0350
• Publications: 21 publications found

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: ClinGen, Orphanet, Genomics England PanelApp, Ambry Genetics

LOC124903011 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 12-108899544-A-G is Benign according to our data. Variant chr12-108899544-A-G is described in ClinVar as Benign. ClinVar VariationId is 1235637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAO	NM_001917.5	c.912+69A>G		intron_variant	Intron 10 of 10	ENST00000228476.8	NP_001908.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAO	ENST00000228476.8	c.912+69A>G		intron_variant	Intron 10 of 10	1	NM_001917.5	ENSP00000228476.3

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52375 AN: 151902 Hom.: 9670 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.380

GnomAD4 exome AF: 0.300 AC: 354430 AN: 1179882 Hom.: 57181 Cov.: 16 AF XY: 0.302 AC XY: 179731 AN XY: 595262

African (AFR) AF: 0.408 AC: 11132 AN: 27252

American (AMR) AF: 0.570 AC: 21871 AN: 38380

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 7344 AN: 23892

East Asian (EAS) AF: 0.469 AC: 16656 AN: 35480

South Asian (SAS) AF: 0.377 AC: 28748 AN: 76236

European-Finnish (FIN) AF: 0.294 AC: 14278 AN: 48496

Middle Eastern (MID) AF: 0.421 AC: 2107 AN: 5006

European-Non Finnish (NFE) AF: 0.270 AC: 236229 AN: 874266

Other (OTH) AF: 0.316 AC: 16065 AN: 50874

GnomAD4 genome AF: 0.345 AC: 52456 AN: 152020 Hom.: 9689 Cov.: 32 AF XY: 0.354 AC XY: 26270 AN XY: 74304

African (AFR) AF: 0.399 AC: 16555 AN: 41454

American (AMR) AF: 0.508 AC: 7757 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1045 AN: 3466

East Asian (EAS) AF: 0.473 AC: 2444 AN: 5172

South Asian (SAS) AF: 0.382 AC: 1838 AN: 4808

European-Finnish (FIN) AF: 0.305 AC: 3221 AN: 10568

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18398 AN: 67974

Other (OTH) AF: 0.382 AC: 808 AN: 2114

Alfa AF: 0.307 Hom.: 4428

Bravo AF: 0.365

Asia WGS AF: 0.415 AC: 1442 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 18, 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	-0.89
CADD	Benign	0.81
DANN	Benign	0.78
PhyloP100		-0.035
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3918347; hg19: chr12-109293320; COSMIC: COSV57322765; COSMIC: COSV57322765;