chr10-125788988-G-A
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_000375.3(UROS):c.678C>T(p.Pro226=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,612,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
UROS
NM_000375.3 synonymous
NM_000375.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.05
Genes affected
UROS (HGNC:12592): (uroporphyrinogen III synthase) The protein encoded by this gene catalyzes the fourth step of porphyrin biosynthesis in the heme biosynthetic pathway. Defects in this gene cause congenital erythropoietic porphyria (Gunther's disease). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
Variant 10-125788988-G-A is Benign according to our data. Variant chr10-125788988-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2866524.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.05 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UROS | NM_000375.3 | c.678C>T | p.Pro226= | synonymous_variant | 10/10 | ENST00000368797.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UROS | ENST00000368797.10 | c.678C>T | p.Pro226= | synonymous_variant | 10/10 | 1 | NM_000375.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000811 AC: 2AN: 246544Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134202
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460590Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726564
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152236Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74368
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 05, 2023 | - - |
Computational scores
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Benign
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Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at