rs76305249

Variant names:

• chr12-108884764-C-T
• rs76305249
• NM_001917.5:c.-9-234C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001917.5(DAO):​c.-9-234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 152,228 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.019 (105 hom., cov: 32)
• Consequence: DAO NM_001917.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.261
• Publications: 0 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: Ambry Genetics, ClinGen, Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-108884764-C-T is Benign according to our data. Variant chr12-108884764-C-T is described in ClinVar as Benign. ClinVar VariationId is 1272817.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0652 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAO	NM_001917.5	MANE Select	c.-9-234C>T		intron	N/A	NP_001908.3
	DAO	NM_001413634.1		c.-9-234C>T		intron	N/A	NP_001400563.1	P14920
	DAO	NM_001413635.1		c.-9-234C>T		intron	N/A	NP_001400564.1	A0A0S2Z3J4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAO	ENST00000228476.8	TSL:1 MANE Select	c.-9-234C>T		intron	N/A	ENSP00000228476.3	P14920
	DAO	ENST00000551281.5	TSL:1	c.-9-234C>T		intron	N/A	ENSP00000446853.1	A0A0B4J250
	DAO	ENST00000547122.5	TSL:1	n.-9-234C>T		intron	N/A	ENSP00000448095.1	A0A0B4J257

Frequencies

GnomAD3 genomes AF: 0.0194 AC: 2948 AN: 152110 Hom.: 104 Cov.: 32

Gnomad AFR AF: 0.0672

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00688

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0194 AC: 2959 AN: 152228 Hom.: 105 Cov.: 32 AF XY: 0.0188 AC XY: 1400 AN XY: 74454

African (AFR) AF: 0.0673 AC: 2794 AN: 41508

American (AMR) AF: 0.00687 AC: 105 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68018

Other (OTH) AF: 0.0142 AC: 30 AN: 2112

Alfa AF: 0.0167 Hom.: 10

Bravo AF: 0.0218

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.66
DANN	Benign	0.75
PhyloP100		-0.26
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: rs76305249; hg19: chr12-109278540;