rs3779084

chr7-50501037-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001082971.2(DDC):c.782-1795T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,116 control chromosomes in the GnomAD database, including 3,653 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3653 hom., cov: 32)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442

Genes affected

DDC (HGNC:2719): (dopa decarboxylase) The encoded protein catalyzes the decarboxylation of L-3,4-dihydroxyphenylalanine (DOPA) to dopamine, L-5-hydroxytryptophan to serotonin and L-tryptophan to tryptamine. Defects in this gene are the cause of aromatic L-amino-acid decarboxylase deficiency (AADCD). AADCD deficiency is an inborn error in neurotransmitter metabolism that leads to combined serotonin and catecholamine deficiency. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jun 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.782-1795T>C		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.782-1795T>C		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32615 AN: 151998 Hom.: 3649 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.214 AC: 32624 AN: 152116 Hom.: 3653 Cov.: 32 AF XY: 0.220 AC XY: 16383 AN XY: 74354

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.188

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.196

Alfa AF: 0.207 Hom.: 1547

Bravo AF: 0.209

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.41
Dann	Benign	0.49

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: rs3779084; hg19: chr7-50568735;