rs11575377
Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The ENST00000444124.7(DDC):c.717G>T(p.Met239Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,612,548 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M239L) has been classified as Likely benign.
Frequency
Consequence
ENST00000444124.7 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DDC | NM_001082971.2 | c.717G>T | p.Met239Ile | missense_variant, splice_region_variant | 7/15 | ENST00000444124.7 | NP_001076440.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DDC | ENST00000444124.7 | c.717G>T | p.Met239Ile | missense_variant, splice_region_variant | 7/15 | 1 | NM_001082971.2 | ENSP00000403644 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00217 AC: 330AN: 152160Hom.: 3 Cov.: 33
GnomAD3 exomes AF: 0.00223 AC: 560AN: 251444Hom.: 2 AF XY: 0.00213 AC XY: 289AN XY: 135900
GnomAD4 exome AF: 0.00171 AC: 2498AN: 1460270Hom.: 14 Cov.: 29 AF XY: 0.00181 AC XY: 1316AN XY: 726588
GnomAD4 genome AF: 0.00217 AC: 330AN: 152278Hom.: 3 Cov.: 33 AF XY: 0.00205 AC XY: 153AN XY: 74458
ClinVar
Submissions by phenotype
Deficiency of aromatic-L-amino-acid decarboxylase Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
DDC-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 09, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2024 | DDC: BP4, BS2 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at