Variant 7-50537910-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PP3_StrongPP5_Moderate

The NM_001082971.2(DDC):c.385C>T(p.Pro129Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DDC
NM_001082971.2 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 9.99

Variant links:

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 links:

DDC-AS1 (HGNC:40171): (DDC antisense RNA 1)

DDC-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 10 ACMG points.

PM1

In a region_of_interest 2 X approximate tandem repeats (size 120) in uniprot entity DDC_HUMAN there are 8 pathogenic changes around while only 1 benign (89%) in NM_001082971.2

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.989

PP5

Variant 7-50537910-G-A is Pathogenic according to our data. Variant chr7-50537910-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3594726.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDC	NM_001082971.2 link	c.385C>T	p.Pro129Ser	missense_variant	4/15	ENST00000444124.7	NP_001076440.2	P20711-1Q53Y41A0A0S2Z3N4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDC	ENST00000444124.7 link	c.385C>T	p.Pro129Ser	missense_variant	4/15	1	NM_001082971.2	ENSP00000403644.2		P20711-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Deficiency of aromatic-L-amino-acid decarboxylase

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Feb 16, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.69

D;.;T;.;.;D;.

Eigen

Pathogenic

0.85

Eigen_PC

Pathogenic

0.77

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.99

.;D;D;D;.;D;D

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.99

D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.20

MutationAssessor

Pathogenic

3.0

M;M;.;.;M;M;M

PrimateAI

Uncertain

0.59

PROVEAN

Pathogenic

-7.6

D;.;.;.;D;D;D

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;.;.;.;T;D;D

Sift4G

Uncertain

0.015

D;D;D;D;D;D;D

Polyphen

1.0

D;.;.;.;.;D;.

Vest4

0.78

MutPred

0.90

Loss of ubiquitination at K130 (P = 0.1166);Loss of ubiquitination at K130 (P = 0.1166);Loss of ubiquitination at K130 (P = 0.1166);.;Loss of ubiquitination at K130 (P = 0.1166);Loss of ubiquitination at K130 (P = 0.1166);Loss of ubiquitination at K130 (P = 0.1166);

MVP

0.91

MPC

0.99

ClinPred

1.0

GERP RS

5.6

Varity_R

0.95

gMVP

0.93

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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