rs3837091

Variant names:

• chr7-50561042-CCTCT-C
• rs3837091
• ENST00000357936.9:c.-61_-58delAGAG

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000357936.9(DDC):​c.-61_-58delAGAG 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
• Publications: 17 publications found

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]

DDC Gene-Disease associations (from GenCC):

• aromatic L-amino acid decarboxylase deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000357936.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	NM_001082971.2	MANE Select	c.-29+4239_-29+4242delAGAG		intron	N/A	NP_001076440.2
	DDC	NM_000790.4		c.-61_-58delAGAG		5_prime_UTR	Exon 1 of 15	NP_000781.2
	DDC	NM_001242886.2		c.-61_-58delAGAG		5_prime_UTR	Exon 1 of 14	NP_001229815.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000357936.9	TSL:1	c.-61_-58delAGAG		5_prime_UTR	Exon 1 of 15	ENSP00000350616.5
	DDC	ENST00000380984.4	TSL:1	c.-61_-58delAGAG		5_prime_UTR	Exon 1 of 10	ENSP00000370371.4
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.-29+4239_-29+4242delAGAG		intron	N/A	ENSP00000403644.2

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

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.250 AC: 1 AN: 4

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.225 AC: 9 AN: 40

Other (OTH) AF: 0.167 AC: 1 AN: 6

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

African (AFR) AF: 0.186 AC: 7698 AN: 41410

American (AMR) AF: 0.220 AC: 3356 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 782 AN: 3466

East Asian (EAS) AF: 0.504 AC: 2569 AN: 5098

South Asian (SAS) AF: 0.316 AC: 1520 AN: 4806

European-Finnish (FIN) AF: 0.283 AC: 2975 AN: 10522

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16653 AN: 67912

Other (OTH) AF: 0.232 AC: 488 AN: 2104

Alfa AF: 0.0974 Hom.: 165

Bravo AF: 0.236

Asia WGS AF: 0.367 AC: 1277 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of aromatic-L-amino-acid decarboxylase (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.81
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3837091; hg19: chr7-50628739; COSMIC: COSV63563419;