rs876661299
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4
The NM_182916.3(TRNT1):c.609-26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,431,606 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 Pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000028 ( 0 hom. )
Consequence
TRNT1
NM_182916.3 intron
NM_182916.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.429
Genes affected
TRNT1 (HGNC:17341): (tRNA nucleotidyl transferase 1) The protein encoded by this gene is a CCA-adding enzyme which belongs to the tRNA nucleotidyltransferase/poly(A) polymerase family. This essential enzyme functions by catalyzing the addition of the conserved nucleotide triplet CCA to the 3' terminus of tRNA molecules. Mutations in this gene result in sideroblastic anemia with B-cell immunodeficiency, periodic fevers, and developmental delay. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
CRBN (HGNC:30185): (cereblon) This gene encodes a protein related to the Lon protease protein family. In rodents and other mammals this gene product is found in the cytoplasm localized with a calcium channel membrane protein, and is thought to play a role in brain development. Mutations in this gene are associated with autosomal recessive nonsyndromic cognitive disability. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 3-3146404-T-C is Pathogenic according to our data. Variant chr3-3146404-T-C is described in ClinVar as [Pathogenic]. Clinvar id is 234935.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-3146404-T-C is described in Lovd as [Likely_pathogenic].
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).. Strength limited to SUPPORTING due to the PP5.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRNT1 | NM_182916.3 | c.609-26T>C | intron_variant | ENST00000251607.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRNT1 | ENST00000251607.11 | c.609-26T>C | intron_variant | 1 | NM_182916.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
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Cov.:
31
GnomAD3 exomes AF: 0.00000851 AC: 2AN: 234992Hom.: 0 AF XY: 0.0000158 AC XY: 2AN XY: 126748
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GnomAD4 exome AF: 0.00000279 AC: 4AN: 1431606Hom.: 0 Cov.: 28 AF XY: 0.00000562 AC XY: 4AN XY: 712308
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GnomAD4 genome ? Cov.: 31
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis pigmentosa and erythrocytic microcytosis Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 26, 2016 | - - |
Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 12, 2022 | For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant is associated with altered splicing resulting in unknown protein product impact (PMID: 26494905). ClinVar contains an entry for this variant (Variation ID: 234935). This variant has been observed in individual(s) with erythrocytic microcytosis and/or non-syndromic retinitis pigmentosa (PMID: 26494905). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change falls in intron 5 of the TRNT1 gene. It does not directly change the encoded amino acid sequence of the TRNT1 protein. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at