rs143483053

Positions:

• chr17-17219122-C-A
• chr17-17219122-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_144997.7(FLCN):​c.959G>T​(p.Arg320Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R320Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FLCN NM_144997.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.09

Genes affected

FLCN (HGNC:27310): (folliculin) This gene is located within the Smith-Magenis syndrome region on chromosome 17. Mutations in this gene are associated with Birt-Hogg-Dube syndrome, which is characterized by fibrofolliculomas, renal tumors, lung cysts, and pneumothorax. Alternative splicing of this gene results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ENSG00000264187 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19916207).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLCN	NM_144997.7	c.959G>T	p.Arg320Leu	missense_variant	9/14	ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9	c.959G>T	p.Arg320Leu	missense_variant	9/14	1	NM_144997.7	ENSP00000285071.4
ENSG00000264187	ENST00000427497.3	n.149-68G>T		intron_variant		1		ENSP00000394249.3
FLCN	ENST00000577591.1	n.-19G>T		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.069	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.49
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.31	T
MutationAssessor	Benign	1.0	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.64	N
REVEL	Uncertain	0.44
Sift	Benign	0.053	T
Sift4G	Benign	0.27	T
Polyphen		0.0	B
Vest4		0.48
MutPred		0.17		Loss of phosphorylation at T323 (P = 0.0489);
MVP		0.54
MPC		0.59
ClinPred		0.17	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.058
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-17122436;