rs138070947
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2
The ENST00000285071.9(FLCN):c.580C>T(p.Arg194Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,613,342 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R194Q) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000285071.9 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FLCN | NM_144997.7 | c.580C>T | p.Arg194Trp | missense_variant | 6/14 | ENST00000285071.9 | NP_659434.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.580C>T | p.Arg194Trp | missense_variant | 6/14 | 1 | NM_144997.7 | ENSP00000285071 | P1 | |
FLCN | ENST00000389169.9 | c.580C>T | p.Arg194Trp | missense_variant | 6/8 | 1 | ENSP00000373821 | |||
FLCN | ENST00000417064.1 | c.421C>T | p.Arg141Trp | missense_variant | 4/4 | 2 | ENSP00000410410 | |||
FLCN | ENST00000480316.1 | n.546C>T | non_coding_transcript_exon_variant | 1/3 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000158 AC: 24AN: 152188Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000192 AC: 48AN: 250438Hom.: 0 AF XY: 0.000192 AC XY: 26AN XY: 135666
GnomAD4 exome AF: 0.000197 AC: 288AN: 1461154Hom.: 1 Cov.: 32 AF XY: 0.000216 AC XY: 157AN XY: 726884
GnomAD4 genome AF: 0.000158 AC: 24AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74360
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 01, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Mar 05, 2022 | - - |
Birt-Hogg-Dube syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jul 18, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 19, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Jul 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 10, 2021 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with a personal history of advanced cancer (Mandelker 2017); This variant is associated with the following publications: (PMID: 29109099, 29181861, 28873162) - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at