Genetic Variant DDO:p.Thr163Ile (chr6-110393313-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001372108.2(DDO):c.488C>T(p.Thr163Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000074 in 1,607,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

DDO
NM_001372108.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.270

Publications

0 publications found

Variant links:

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]

DDO links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18533015).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDO	NM_001372108.2	MANE Select	c.488C>T	p.Thr163Ile	missense	Exon 5 of 5	NP_001359037.1	Q99489-1
DDO	NM_001368170.1		c.326C>T	p.Thr109Ile	missense	Exon 6 of 6	NP_001355099.1
DDO	NM_004032.3		c.311C>T	p.Thr104Ile	missense	Exon 4 of 4	NP_004023.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DDO	ENST00000368924.9	TSL:1 MANE Select	c.488C>T	p.Thr163Ile	missense	Exon 5 of 5	ENSP00000357920.4	Q99489-1
DDO	ENST00000854440.1		c.488C>T	p.Thr163Ile	missense	Exon 6 of 6	ENSP00000524499.1
DDO	ENST00000854441.1		c.488C>T	p.Thr163Ile	missense	Exon 6 of 6	ENSP00000524500.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000200

AC:

AN:

249620

AF XY:

0.0000370

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000442

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000790

AC:

115

AN:

1455044

Hom.:

Cov.:

AF XY:

0.0000817

AC XY:

AN XY:

722562

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33352

American (AMR)

AF:

0.00

AC:

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39494

South Asian (SAS)

AF:

0.00

AC:

AN:

86134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000100

AC:

111

AN:

1107016

Other (OTH)

AF:

0.0000666

AC:

AN:

60080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68052

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000565

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.48

CADD

Benign

3.0

(source)

DANN

Benign

0.83

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.54

M_CAP

Benign

0.037

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.85

PhyloP100

0.27

PrimateAI

Benign

0.35

PROVEAN

Benign

-2.0

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Benign

0.21

Polyphen

0.0060

Vest4

0.045

MutPred

0.51

Loss of sheet (P = 0.0817)

MVP

0.40

MPC

0.041

ClinPred

0.058

GERP RS

0.68

gMVP

0.39

Mutation Taster

=87/13

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over