rs3837091

Positions:

• chr7-50561042-CCTCT-C
• chr7-50561042-CCTCT-CCT
• chr7-50561042-CCTCT-CCTCTCTCT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000357936.9(DDC):​c.-61_-58del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 151,836 control chromosomes in the GnomAD database, including 4,587 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4586 hom., cov: 24)
  • Exomes 𝑓: 0.20 (1 hom.)
• Consequence: DDC ENST00000357936.9 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.812

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 -10 ACMG points.

• BP6: Variant 7-50561042-CCTCT-C is Benign according to our data. Variant chr7-50561042-CCTCT-C is described in ClinVar as [Benign]. Clinvar id is 360446.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2	c.-29+4239_-29+4242del		intron_variant		ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.-29+4239_-29+4242del		intron_variant		1	NM_001082971.2	ENSP00000403644	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36363 AN: 151660 Hom.: 4582 Cov.: 24

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.505

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.283

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.229

GnomAD4 exome AF: 0.200 AC: 12 AN: 60 Hom.: 1 AF XY: 0.125 AC XY: 5 AN XY: 40

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.250

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.225

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.240 AC: 36365 AN: 151776 Hom.: 4586 Cov.: 24 AF XY: 0.243 AC XY: 18027 AN XY: 74146

Gnomad4 AFR AF: 0.186

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.504

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.283

Gnomad4 NFE AF: 0.245

Gnomad4 OTH AF: 0.232

Alfa AF: 0.0974 Hom.: 165

Bravo AF: 0.236

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Deficiency of aromatic-L-amino-acid decarboxylase Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs3837091; hg19: chr7-50628739;