chr17-17217090-C-A
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_144997.7(FLCN):c.1155G>T(p.Gln385His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,276 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Q385Q) has been classified as Likely benign.
Frequency
Consequence
NM_144997.7 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLCN | NM_144997.7 | c.1155G>T | p.Gln385His | missense_variant | 10/14 | ENST00000285071.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLCN | ENST00000285071.9 | c.1155G>T | p.Gln385His | missense_variant | 10/14 | 1 | NM_144997.7 | P1 | |
MPRIP | ENST00000578209.5 | c.*18-400C>A | intron_variant | 3 | |||||
FLCN | ENST00000577591.1 | n.178G>T | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000335 AC: 51AN: 152272Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251056Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135804
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461004Hom.: 0 Cov.: 31 AF XY: 0.0000261 AC XY: 19AN XY: 726870
GnomAD4 genome AF: 0.000335 AC: 51AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16AN XY: 74392
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 01, 2018 | 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 | Oct 22, 2021 | - - |
FLCN-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 30, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Birt-Hogg-Dube syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at