rs1394870596

Variant names:

• chr6-110393226-C-G
• rs1394870596
• NM_001372108.2:c.575G>C

Your query was ambiguous. Multiple possible variants found:

• chr6-110393226-C-G
• chr6-110393226-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001372108.2(DDO):​c.575G>C​(p.Gly192Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,228 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G192E) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: DDO NM_001372108.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.67

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDO	NM_001372108.2	c.575G>C	p.Gly192Ala	missense_variant	Exon 5 of 5	ENST00000368924.9	NP_001359037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDO	ENST00000368924.9	c.575G>C	p.Gly192Ala	missense_variant	Exon 5 of 5	1	NM_001372108.2	ENSP00000357920.4
DDO	ENST00000368923.8	c.398G>C	p.Gly133Ala	missense_variant	Exon 4 of 4	2		ENSP00000357919.4
DDO	ENST00000479373.1	n.*217G>C		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000436642.1
DDO	ENST00000479373.1	n.*217G>C		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000436642.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 33

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: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 33

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152228 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74368

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.022	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Benign	0.97
Eigen	Uncertain	0.25
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.79	T;T
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Uncertain	-0.076	T
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.2	N;N
REVEL	Uncertain	0.46
Sift	Benign	0.33	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.96	D;P
Vest4		0.42
MutPred		0.47		Loss of catalytic residue at A219 (P = 0.0713);.;
MVP		0.85
MPC		0.19
ClinPred		0.72	D
GERP RS		5.0
gMVP		0.75

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

LitVar

Other links and lift over

dbSNP: rs1394870596; hg19: chr6-110714429;