NM_001128228.3:c.1827_1844dupGGAGGAGGAGGAGGAGGA
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001128228.3(TPRN):c.1827_1844dupGGAGGAGGAGGAGGAGGA(p.Glu610_Glu615dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000028 in 1,608,424 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001128228.3 disruptive_inframe_insertion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TPRN | ENST00000409012.6 | c.1827_1844dupGGAGGAGGAGGAGGAGGA | p.Glu610_Glu615dup | disruptive_inframe_insertion | Exon 2 of 4 | 1 | NM_001128228.3 | ENSP00000387100.4 | ||
TPRN | ENST00000477345.1 | n.2548_2565dupGGAGGAGGAGGAGGAGGA | non_coding_transcript_exon_variant | Exon 1 of 3 | 1 | |||||
TPRN | ENST00000333046.8 | c.1221_1238dupGGAGGAGGAGGAGGAGGA | p.Glu408_Glu413dup | disruptive_inframe_insertion | Exon 2 of 3 | 2 | ENSP00000327617.4 | |||
TPRN | ENST00000541945.1 | n.*62_*79dupGGAGGAGGAGGAGGAGGA | downstream_gene_variant | 4 |
Frequencies
GnomAD3 genomes AF: 0.0000595 AC: 9AN: 151158Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000247 AC: 36AN: 1457154Hom.: 0 Cov.: 31 AF XY: 0.0000235 AC XY: 17AN XY: 724714
GnomAD4 genome AF: 0.0000595 AC: 9AN: 151270Hom.: 0 Cov.: 33 AF XY: 0.0000541 AC XY: 4AN XY: 73908
ClinVar
Submissions by phenotype
not provided Uncertain:1
Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with TPRN-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.1827_1844dup, results in the insertion of 6 amino acid(s) of the TPRN protein (p.Glu616_Glu621dup), but otherwise preserves the integrity of the reading frame. -
TPRN-related disorder Uncertain:1
The TPRN c.1827_1844dup18 variant is predicted to result in an in-frame duplication (p.Glu616_Glu621dup). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at