12-108887351-C-T

Variant names:

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

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.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
• Publications: 2 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 -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 VariationId 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.

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.195-99C>T		intron	N/A	NP_001908.3
	DAO	NM_001413634.1		c.195-99C>T		intron	N/A	NP_001400563.1	P14920
	DAO	NM_001413635.1		c.195-99C>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.195-99C>T		intron	N/A	ENSP00000228476.3	P14920
	DAO	ENST00000551281.5	TSL:1	c.195-99C>T		intron	N/A	ENSP00000446853.1	A0A0B4J250
	DAO	ENST00000547122.5	TSL:1	n.195-2118C>T		intron	N/A	ENSP00000448095.1	A0A0B4J257

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

African (AFR) AF: 0.206 AC: 3962 AN: 19260

American (AMR) AF: 0.0209 AC: 915 AN: 43774

Ashkenazi Jewish (ASJ) AF: 0.0226 AC: 486 AN: 21532

East Asian (EAS) AF: 0.0000824 AC: 3 AN: 36394

South Asian (SAS) AF: 0.0190 AC: 1352 AN: 71260

European-Finnish (FIN) AF: 0.0130 AC: 686 AN: 52676

Middle Eastern (MID) AF: 0.0449 AC: 191 AN: 4250

European-Non Finnish (NFE) AF: 0.0178 AC: 7812 AN: 437986

Other (OTH) AF: 0.0315 AC: 1133 AN: 36004

GnomAD4 genome AF: 0.0697 AC: 10598 AN: 152134 Hom.: 891 Cov.: 32 AF XY: 0.0662 AC XY: 4924 AN XY: 74366

African (AFR) AF: 0.204 AC: 8470 AN: 41472

American (AMR) AF: 0.0309 AC: 472 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5182

South Asian (SAS) AF: 0.0189 AC: 91 AN: 4820

European-Finnish (FIN) AF: 0.0139 AC: 147 AN: 10596

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0176 AC: 1197 AN: 67996

Other (OTH) AF: 0.0573 AC: 121 AN: 2110

Alfa AF: 0.0303 Hom.: 104

Bravo AF: 0.0775

Asia WGS AF: 0.0480 AC: 167 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.1
DANN	Benign	0.72
PhyloP100		0.67
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: rs75861794; hg19: chr12-109281127;