NM_001082971.2:c.*341C>T

Variant names:

• chr7-50458521-G-A
• rs11575553
• NM_001082971.2:c.*341C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001082971.2(DDC):​c.*341C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 152,230 control chromosomes in the GnomAD database, including 704 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (704 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: DDC NM_001082971.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.749
• Publications: 16 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: Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, G2P, Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 7-50458521-G-A is Benign according to our data. Variant chr7-50458521-G-A is described in ClinVar as Benign. ClinVar VariationId is 360423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.098 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001082971.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	NM_001082971.2	MANE Select	c.*341C>T		3_prime_UTR	Exon 15 of 15	NP_001076440.2	A0A0S2Z3N4
	DDC	NM_000790.4		c.*341C>T		3_prime_UTR	Exon 15 of 15	NP_000781.2	P20711-1
	DDC	NM_001242886.2		c.*341C>T		3_prime_UTR	Exon 14 of 14	NP_001229815.2	A0A087WV24

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDC	ENST00000444124.7	TSL:1 MANE Select	c.*341C>T		3_prime_UTR	Exon 15 of 15	ENSP00000403644.2	P20711-1
	DDC	ENST00000357936.9	TSL:1	c.*341C>T		3_prime_UTR	Exon 15 of 15	ENSP00000350616.5	P20711-1
	DDC	ENST00000897740.1		c.*341C>T		3_prime_UTR	Exon 16 of 16	ENSP00000567799.1

Frequencies

GnomAD3 genomes AF: 0.0794 AC: 12079 AN: 152112 Hom.: 702 Cov.: 33

Gnomad AFR AF: 0.0245

Gnomad AMI AF: 0.0515

Gnomad AMR AF: 0.0971

Gnomad ASJ AF: 0.0545

Gnomad EAS AF: 0.0707

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0914

Gnomad OTH AF: 0.0708

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0794 AC: 12083 AN: 152230 Hom.: 704 Cov.: 33 AF XY: 0.0853 AC XY: 6346 AN XY: 74426

African (AFR) AF: 0.0244 AC: 1015 AN: 41554

American (AMR) AF: 0.0973 AC: 1488 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0545 AC: 189 AN: 3466

East Asian (EAS) AF: 0.0711 AC: 368 AN: 5178

South Asian (SAS) AF: 0.106 AC: 509 AN: 4822

European-Finnish (FIN) AF: 0.198 AC: 2091 AN: 10572

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0914 AC: 6218 AN: 68022

Other (OTH) AF: 0.0696 AC: 147 AN: 2112

Alfa AF: 0.0835 Hom.: 784

Bravo AF: 0.0707

Asia WGS AF: 0.0690 AC: 240 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Deficiency of aromatic-L-amino-acid decarboxylase (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.22
DANN	Benign	0.32
PhyloP100		-0.75
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: rs11575553; hg19: chr7-50526219;