rs3829897

chr7-50562067-G-T

Variant summary

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

The NM_001082971.2(DDC):c.-29+3218C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,016 control chromosomes in the GnomAD database, including 17,329 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 0.47 (17329 hom., cov: 33)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.604 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.-29+3218C>A		intron_variant		ENST00000444124.7
DDC	XM_005271745.5	c.-29+3218C>A		intron_variant
DDC	XM_047419931.1	c.-29+3218C>A		intron_variant
DDC	XM_047419932.1	c.-29+3218C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.-29+3218C>A		intron_variant		1	NM_001082971.2	P1
DDC	ENST00000420203.1	c.-29+1928C>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70963 AN: 151898 Hom.: 17301 Cov.: 33

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.623

Gnomad SAS AF: 0.504

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.467 AC: 71042 AN: 152016 Hom.: 17329 Cov.: 33 AF XY: 0.477 AC XY: 35408 AN XY: 74306

Gnomad4 AFR AF: 0.586

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.323

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.389

Gnomad4 OTH AF: 0.422

Alfa AF: 0.412 Hom.: 7450

Bravo AF: 0.465

Asia WGS AF: 0.515 AC: 1790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.27
Dann	Benign	0.39

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3829897; hg19: chr7-50629764; COSMIC: COSV63566029; COSMIC: COSV63566029;