chr4-16163431-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_153365.3(TAPT1):c.1581G>C(p.Leu527Phe) 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 1,461,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L527L) has been classified as Likely benign.
Frequency
Consequence
NM_153365.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAPT1 | NM_153365.3 | c.1581G>C | p.Leu527Phe | missense_variant | 14/14 | ENST00000405303.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAPT1 | ENST00000405303.7 | c.1581G>C | p.Leu527Phe | missense_variant | 14/14 | 1 | NM_153365.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249226Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135202
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461668Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727118
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 03, 2021 | This sequence change replaces leucine with phenylalanine at codon 527 of the TAPT1 protein (p.Leu527Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs777380785, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with TAPT1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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