rs527331900
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2
The NM_182916.3(TRNT1):c.810_811insAAACTT(p.Pro270_Ala271insLysLeu) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,613,238 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00067 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00053 ( 4 hom. )
Consequence
TRNT1
NM_182916.3 inframe_insertion
NM_182916.3 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.649
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 Benign. Variant got -14 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_182916.3.
BP6
?
Variant 3-3147456-C-CTAAACT is Benign according to our data. Variant chr3-3147456-C-CTAAACT is described in ClinVar as [Likely_benign]. Clinvar id is 475270.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00067 (102/152204) while in subpopulation EAS AF= 0.016 (83/5182). AF 95% confidence interval is 0.0132. There are 1 homozygotes in gnomad4. There are 52 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 4 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRNT1 | NM_182916.3 | c.810_811insAAACTT | p.Pro270_Ala271insLysLeu | inframe_insertion | 7/8 | ENST00000251607.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TRNT1 | ENST00000251607.11 | c.810_811insAAACTT | p.Pro270_Ala271insLysLeu | inframe_insertion | 7/8 | 1 | NM_182916.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000671 AC: 102AN: 152086Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00131 AC: 329AN: 250712Hom.: 2 AF XY: 0.00144 AC XY: 195AN XY: 135560
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GnomAD4 exome AF: 0.000531 AC: 776AN: 1461034Hom.: 4 Cov.: 32 AF XY: 0.000578 AC XY: 420AN XY: 726800
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GnomAD4 genome ? AF: 0.000670 AC: 102AN: 152204Hom.: 1 Cov.: 33 AF XY: 0.000699 AC XY: 52AN XY: 74416
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:5
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 13, 2018 | - - |
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 01, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | TRNT1: PM4, BS1, BS2 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Retinal dystrophy Benign:1
Benign, criteria provided, single submitter | research | Dept Of Ophthalmology, Nagoya University | Oct 01, 2023 | - - |
Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at