rs3735273

chr7-50529166-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001082971.2(DDC):c.570+42G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,610,546 control chromosomes in the GnomAD database, including 49,259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.27 (5918 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43341 hom.)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.48

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-50529166-C-T is Benign according to our data. Variant chr7-50529166-C-T is described in ClinVar as [Benign]. Clinvar id is 1256784.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDC	NM_001082971.2	c.570+42G>A		intron_variant		ENST00000444124.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDC	ENST00000444124.7	c.570+42G>A		intron_variant		1	NM_001082971.2	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40997 AN: 151902 Hom.: 5907 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.255

GnomAD3 exomes AF: 0.246 AC: 61918 AN: 251274 Hom.: 8413 AF XY: 0.252 AC XY: 34201 AN XY: 135830

Gnomad AFR exome AF: 0.363

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.202

Gnomad EAS exome AF: 0.404

Gnomad SAS exome AF: 0.314

Gnomad FIN exome AF: 0.210

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.222

GnomAD4 exome AF: 0.239 AC: 349002 AN: 1458528 Hom.: 43341 Cov.: 32 AF XY: 0.242 AC XY: 175589 AN XY: 725654

Gnomad4 AFR exome AF: 0.363

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.381

Gnomad4 SAS exome AF: 0.315

Gnomad4 FIN exome AF: 0.217

Gnomad4 NFE exome AF: 0.230

Gnomad4 OTH exome AF: 0.256

GnomAD4 genome AF: 0.270 AC: 41032 AN: 152018 Hom.: 5918 Cov.: 32 AF XY: 0.268 AC XY: 19915 AN XY: 74320

Gnomad4 AFR AF: 0.358

Gnomad4 AMR AF: 0.185

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.235

Gnomad4 OTH AF: 0.258

Alfa AF: 0.256 Hom.: 1583

Bravo AF: 0.271

Asia WGS AF: 0.333 AC: 1158 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 26, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.72
Dann	Benign	0.51

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: rs3735273; hg19: chr7-50596864; COSMIC: COSV63567855; COSMIC: COSV63567855;