9-137192278-G-A
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_001128228.3(TPRN):c.2054C>T(p.Pro685Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001128228.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPRN | NM_001128228.3 | c.2054C>T | p.Pro685Leu | missense_variant | 3/4 | ENST00000409012.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPRN | ENST00000409012.6 | c.2054C>T | p.Pro685Leu | missense_variant | 3/4 | 1 | NM_001128228.3 | P1 | |
TPRN | ENST00000477345.1 | n.2775C>T | non_coding_transcript_exon_variant | 2/3 | 1 | ||||
TPRN | ENST00000333046.8 | c.1448C>T | p.Pro483Leu | missense_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249396Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135398
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460708Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726672
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 19, 2022 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 685 of the TPRN protein (p.Pro685Leu). This variant is present in population databases (rs778804291, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TPRN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at