NM_001917.5:c.279G>A

Variant names:

• chr12-108887534-G-A
• rs7980427
• NM_001917.5:c.279G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001917.5(DAO):​c.279G>A​(p.Ser93Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0911 in 1,613,036 control chromosomes in the GnomAD database, including 9,252 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (2294 hom., cov: 32)
  • Exomes 𝑓: 0.086 (6958 hom.)
• Consequence: DAO NM_001917.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.816
• Publications: 14 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, Genomics England PanelApp, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 12-108887534-G-A is Benign according to our data. Variant chr12-108887534-G-A is described in ClinVar as Benign. ClinVar VariationId is 1279421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.816 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.296 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.279G>A	p.Ser93Ser	synonymous	Exon 3 of 11	NP_001908.3
	DAO	NM_001413634.1		c.279G>A	p.Ser93Ser	synonymous	Exon 4 of 12	NP_001400563.1	P14920
	DAO	NM_001413635.1		c.279G>A	p.Ser93Ser	synonymous	Exon 3 of 10	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.279G>A	p.Ser93Ser	synonymous	Exon 3 of 11	ENSP00000228476.3	P14920
	DAO	ENST00000551281.5	TSL:1	c.279G>A	p.Ser93Ser	synonymous	Exon 3 of 8	ENSP00000446853.1	A0A0B4J250
	DAO	ENST00000547122.5	TSL:1	n.195-1935G>A		intron	N/A	ENSP00000448095.1	A0A0B4J257

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21013 AN: 151826 Hom.: 2284 Cov.: 32

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.00290

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.0616

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0769

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.0948 AC: 23843 AN: 251454 AF XY: 0.0966

Gnomad AFR exome AF: 0.307

Gnomad AMR exome AF: 0.0570

Gnomad ASJ exome AF: 0.112

Gnomad EAS exome AF: 0.00103

Gnomad FIN exome AF: 0.0541

Gnomad NFE exome AF: 0.0795

Gnomad OTH exome AF: 0.0956

GnomAD4 exome AF: 0.0862 AC: 125973 AN: 1461092 Hom.: 6958 Cov.: 31 AF XY: 0.0880 AC XY: 63961 AN XY: 726902

African (AFR) AF: 0.315 AC: 10533 AN: 33422

American (AMR) AF: 0.0590 AC: 2640 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2856 AN: 26126

East Asian (EAS) AF: 0.000630 AC: 25 AN: 39698

South Asian (SAS) AF: 0.157 AC: 13509 AN: 86224

European-Finnish (FIN) AF: 0.0542 AC: 2894 AN: 53418

Middle Eastern (MID) AF: 0.160 AC: 925 AN: 5764

European-Non Finnish (NFE) AF: 0.0782 AC: 86937 AN: 1111354

Other (OTH) AF: 0.0937 AC: 5654 AN: 60362

GnomAD4 genome AF: 0.139 AC: 21054 AN: 151944 Hom.: 2294 Cov.: 32 AF XY: 0.136 AC XY: 10121 AN XY: 74284

African (AFR) AF: 0.301 AC: 12434 AN: 41372

American (AMR) AF: 0.0768 AC: 1172 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 371 AN: 3468

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5168

South Asian (SAS) AF: 0.148 AC: 714 AN: 4810

European-Finnish (FIN) AF: 0.0616 AC: 652 AN: 10582

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.0769 AC: 5230 AN: 67984

Other (OTH) AF: 0.128 AC: 269 AN: 2108

Alfa AF: 0.0973 Hom.: 1719

Bravo AF: 0.146

Asia WGS AF: 0.111 AC: 388 AN: 3478

EpiCase AF: 0.0845

EpiControl AF: 0.0826

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DAO-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.8
DANN	Benign	0.73
PhyloP100		-0.82
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs7980427; hg19: chr12-109281310;