chr1-45012913-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000374.5(UROD):āc.27G>Cā(p.Gln9His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000936 in 1,613,150 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 (ā ā ).
Frequency
Consequence
NM_000374.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UROD | NM_000374.5 | c.27G>C | p.Gln9His | missense_variant | 2/10 | ENST00000246337.9 | |
UROD | NR_036510.2 | n.89G>C | non_coding_transcript_exon_variant | 2/10 | |||
UROD | NR_158184.1 | n.89G>C | non_coding_transcript_exon_variant | 2/10 | |||
UROD | NR_158185.1 | n.39G>C | non_coding_transcript_exon_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UROD | ENST00000246337.9 | c.27G>C | p.Gln9His | missense_variant | 2/10 | 1 | NM_000374.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000593 AC: 9AN: 151786Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251066Hom.: 0 AF XY: 0.0000810 AC XY: 11AN XY: 135772
GnomAD4 exome AF: 0.0000972 AC: 142AN: 1461364Hom.: 0 Cov.: 36 AF XY: 0.0000949 AC XY: 69AN XY: 727004
GnomAD4 genome AF: 0.0000593 AC: 9AN: 151786Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74100
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 13, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 874337). This missense change has been observed in individual(s) with porphyria cutanea tarda (PMID: 30514647). This variant is present in population databases (rs150027651, gnomAD 0.009%). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 9 of the UROD protein (p.Gln9His). - |
Familial porphyria cutanea tarda Uncertain:1
Uncertain significance, 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at