NM_001372108.2:c.413C>T

Variant names:

• chr6-110404819-G-A
• rs1159089293
• NM_001372108.2:c.413C>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001372108.2(DDO):​c.413C>T​(p.Thr138Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DDO NM_001372108.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.57
• Publications: 0 publications found

Genes affected

DDO (HGNC:2727): (D-aspartate oxidase) The protein encoded by this gene is a peroxisomal flavoprotein that catalyzes the oxidative deamination of D-aspartate and N-methyl D-aspartate. Flavin adenine dinucleotide or 6-hydroxyflavin adenine dinucleotide can serve as the cofactor in this reaction. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2019]

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.941

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372108.2. 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
	DDO	NM_001372108.2	MANE Select	c.413C>T	p.Thr138Ile	missense	Exon 4 of 5	NP_001359037.1	Q99489-1
	DDO	NM_001368170.1		c.251C>T	p.Thr84Ile	missense	Exon 5 of 6	NP_001355099.1
	DDO	NM_001368174.1		c.59C>T	p.Thr20Ile	missense	Exon 4 of 5	NP_001355103.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDO	ENST00000368924.9	TSL:1 MANE Select	c.413C>T	p.Thr138Ile	missense	Exon 4 of 5	ENSP00000357920.4	Q99489-1
	DDO	ENST00000854440.1		c.413C>T	p.Thr138Ile	missense	Exon 5 of 6	ENSP00000524499.1
	DDO	ENST00000854441.1		c.413C>T	p.Thr138Ile	missense	Exon 5 of 6	ENSP00000524500.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Pathogenic	28
DANN	Pathogenic	1.0
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.88
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	D
M_CAP	Uncertain	0.12	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-0.34	T
PhyloP100		9.6
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Pathogenic	0.82
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.95
MutPred		0.81		Gain of methylation at K168 (P = 0.0653)
MVP		0.65
MPC		0.29
ClinPred		1.0	D
GERP RS		5.6
gMVP		0.83
Mutation Taster		=27/73	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1159089293; hg19: chr6-110726022;