chr3-3129165-CAGA-C
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4_SupportingPP5
The NM_182916.3(TRNT1):c.128_130delAAG(p.Glu43del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000026 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_182916.3 disruptive_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRNT1 | NM_182916.3 | c.128_130delAAG | p.Glu43del | disruptive_inframe_deletion | Exon 2 of 8 | ENST00000251607.11 | NP_886552.3 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152184Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251448Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135912
GnomAD4 exome AF: 0.0000239 AC: 35AN: 1461810Hom.: 0 AF XY: 0.0000193 AC XY: 14AN XY: 727202
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152184Hom.: 0 Cov.: 34 AF XY: 0.0000538 AC XY: 4AN XY: 74334
ClinVar
Submissions by phenotype
not provided Pathogenic:1Uncertain:1
In-frame deletion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 36819107, 26494905) -
PM4 -
Retinitis pigmentosa and erythrocytic microcytosis Pathogenic:1
- -
Congenital sideroblastic anemia-B-cell immunodeficiency-periodic fever-developmental delay syndrome Pathogenic:1
This variant, c.128_130del, results in the deletion of 1 amino acid(s) of the TRNT1 protein (p.Glu43del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs765128768, gnomAD 0.006%). This variant has been observed in individual(s) with clinical features of TRNT1-related disorders (PMID: 26494905, 28390992; internal data). 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 also known as c.126_128delAGA. ClinVar contains an entry for this variant (Variation ID: 234932). For these reasons, this variant has been classified as Pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at