rs760663364
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_000110.4(DPYD):c.1538C>T(p.Ala513Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,612,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A513G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000110.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DPYD | NM_000110.4 | c.1538C>T | p.Ala513Val | missense_variant | 13/23 | ENST00000370192.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DPYD | ENST00000370192.8 | c.1538C>T | p.Ala513Val | missense_variant | 13/23 | 1 | NM_000110.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151902Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250216Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135256
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1460352Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726510
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151902Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74174
ClinVar
Submissions by phenotype
Dihydropyrimidine dehydrogenase deficiency Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | May 15, 2018 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 24, 2022 | The c.1538C>T (p.A513V) alteration is located in exon 13 (coding exon 13) of the DPYD gene. This alteration results from a C to T substitution at nucleotide position 1538, causing the alanine (A) at amino acid position 513 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at