9-137192293-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001128228.3(TPRN):c.2039C>T(p.Pro680Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000304 in 1,612,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. P680P) has been classified as Likely benign.
Frequency
Consequence
NM_001128228.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TPRN | NM_001128228.3 | c.2039C>T | p.Pro680Leu | missense_variant | 3/4 | ENST00000409012.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TPRN | ENST00000409012.6 | c.2039C>T | p.Pro680Leu | missense_variant | 3/4 | 1 | NM_001128228.3 | P1 | |
TPRN | ENST00000477345.1 | n.2760C>T | non_coding_transcript_exon_variant | 2/3 | 1 | ||||
TPRN | ENST00000333046.8 | c.1433C>T | p.Pro478Leu | missense_variant | 3/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152176Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.0000315 AC: 46AN: 1460652Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 726652
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74350
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 20, 2021 | The c.2039C>T (p.P680L) alteration is located in exon 3 (coding exon 3) of the TPRN gene. This alteration results from a C to T substitution at nucleotide position 2039, causing the proline (P) at amino acid position 680 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at