rs876658621
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_144997.7(FLCN):c.844A>T(p.Thr282Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,434 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T282I) has been classified as Uncertain significance.
Frequency
Consequence
NM_144997.7 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 |
---|---|---|---|---|---|---|---|
FLCN | NM_144997.7 | c.844A>T | p.Thr282Ser | missense_variant | 8/14 | ENST00000285071.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.844A>T | p.Thr282Ser | missense_variant | 8/14 | 1 | NM_144997.7 | P1 | |
FLCN | ENST00000389169.9 | c.844A>T | p.Thr282Ser | missense_variant | 8/8 | 1 | |||
FLCN | ENST00000466317.1 | n.687A>T | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
FLCN | ENST00000480316.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000400 AC: 1AN: 250102Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135416
GnomAD4 exome AF: 0.00000822 AC: 12AN: 1460350Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6AN XY: 726598
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152084Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 29, 2024 | The p.T282S variant (also known as c.844A>T), located in coding exon 5 of the FLCN gene, results from an A to T substitution at nucleotide position 844. The threonine at codon 282 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Birt-Hogg-Dube syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 282 of the FLCN protein (p.Thr282Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 230538). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FLCN protein function with a negative predictive value of 80%. 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