Variant 6-110404798-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001372108.2(DDO):c.434C>T(p.Ala145Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

DDO
NM_001372108.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.170

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:

DDO (HGNC:):

DDO links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10000914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDO	NM_001372108.2 linkuse as main transcript	c.434C>T	p.Ala145Val	missense_variant	4/5	ENST00000368924.9	NP_001359037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DDO	ENST00000368924.9 linkuse as main transcript	c.434C>T	p.Ala145Val	missense_variant	4/5	1	NM_001372108.2	ENSP00000357920.4	Q99489-1
DDO	ENST00000368923.8 linkuse as main transcript	c.281+3536C>T		intron_variant		2		ENSP00000357919.4	Q99489-2
DDO	ENST00000479373.1 linkuse as main transcript	n.*76C>T		non_coding_transcript_exon_variant	3/4	5		ENSP00000436642.1	F2Z2E0
DDO	ENST00000479373.1 linkuse as main transcript	n.*76C>T		3_prime_UTR_variant	3/4	5		ENSP00000436642.1	F2Z2E0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2024

The c.518C>T (p.A173V) alteration is located in exon 4 (coding exon 4) of the DDO gene. This alteration results from a C to T substitution at nucleotide position 518, causing the alanine (A) at amino acid position 173 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.50

CADD

Benign

5.5

DANN

Uncertain

0.98

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.83

M_CAP

Benign

0.017

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.97

PrimateAI

Benign

0.20

PROVEAN

Benign

-1.2

REVEL

Benign

0.15

Sift

Benign

0.36

Sift4G

Benign

0.35

Polyphen

0.0

Vest4

0.14

MutPred

0.44

Gain of methylation at K168 (P = 0.1252);

MVP

0.25

MPC

0.038

ClinPred

0.060

GERP RS

-0.22

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over