chr1-45012897-T-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PP3_StrongBP6_Moderate
The NM_000374.5(UROD):c.21-10T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.20 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
UROD
NM_000374.5 splice_polypyrimidine_tract, intron
NM_000374.5 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9999
2
Clinical Significance
Conservation
PhyloP100: 0.445
Genes affected
UROD (HGNC:12591): (uroporphyrinogen decarboxylase) This gene encodes an enzyme in the heme biosynthetic pathway. This enzyme is responsible for catalyzing the conversion of uroporphyrinogen to coproporphyrinogen through the removal of four carboxymethyl side chains. Mutations and deficiency in this enzyme are known to cause familial porphyria cutanea tarda and hepatoerythropoetic porphyria.[provided by RefSeq, Aug 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 1-45012897-T-A is Benign according to our data. Variant chr1-45012897-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 3061020.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UROD | NM_000374.5 | c.21-10T>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000246337.9 | |||
UROD | NR_036510.2 | n.73T>A | non_coding_transcript_exon_variant | 2/10 | |||
UROD | NR_158184.1 | n.73T>A | non_coding_transcript_exon_variant | 2/10 | |||
UROD | NR_158185.1 | n.33-10T>A | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UROD | ENST00000246337.9 | c.21-10T>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000374.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 278AN: 141466Hom.: 0 Cov.: 32 FAILED QC
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32
FAILED QC
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.195 AC: 161783AN: 828142Hom.: 0 Cov.: 41 AF XY: 0.180 AC XY: 76742AN XY: 426990
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Data not reliable, filtered out with message: AS_VQSR
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GnomAD4 genome ? Data not reliable, filtered out with message: AS_VQSR AF: 0.00196 AC: 278AN: 141562Hom.: 0 Cov.: 32 AF XY: 0.00218 AC XY: 150AN XY: 68718
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?
Data not reliable, filtered out with message: AS_VQSR
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
UROD-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 08, 2023 | 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). - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
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dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
DS_AL_spliceai
Position offset: 10
Find out detailed SpliceAI scores and Pangolin per-transcript scores at