rs10499693

Positions:

• chr7-50469600-G-A
• chr7-50469600-G-C

Variant summary

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

The NM_001082971.2(DDC):​c.1140+473C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0528 in 152,208 control chromosomes in the GnomAD database, including 492 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 0.053 (492 hom., cov: 31)
• Consequence: DDC NM_001082971.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2	c.1140+473C>T		intron_variant		ENST00000444124.7	NP_001076440.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7	c.1140+473C>T		intron_variant		1	NM_001082971.2	ENSP00000403644	P1

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 8007 AN: 152090 Hom.: 487 Cov.: 31

Gnomad AFR AF: 0.148

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0289

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0137

Gnomad FIN AF: 0.00754

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0171

Gnomad OTH AF: 0.0373

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

GnomAD4 genome AF: 0.0528 AC: 8042 AN: 152208 Hom.: 492 Cov.: 31 AF XY: 0.0508 AC XY: 3784 AN XY: 74440

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.0289

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.00754

Gnomad4 NFE AF: 0.0171

Gnomad4 OTH AF: 0.0369

Alfa AF: 0.0195 Hom.: 21

Bravo AF: 0.0581

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.39

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: rs10499693; hg19: chr7-50537298;