17-17213816-G-C

Variant names:

• chr17-17213816-G-C
• rs879255683
• NM_144997.7:c.1579C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_144997.7(FLCN):​c.1579C>G​(p.Arg527Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. R527Q) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLCN NM_144997.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• Publications: 0 publications found

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:):

MPRIP (HGNC:30321): (myosin phosphatase Rho interacting protein) Enables cadherin binding activity. Predicted to be involved in actin filament organization. Located in actin cytoskeleton and cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144997.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLCN	NM_144997.7	MANE Select	c.1579C>G	p.Arg527Gly	missense	Exon 14 of 14	NP_659434.2
	FLCN	NM_001353229.2		c.1633C>G	p.Arg545Gly	missense	Exon 16 of 16	NP_001340158.1
	FLCN	NM_001353230.2		c.1579C>G	p.Arg527Gly	missense	Exon 15 of 15	NP_001340159.1	Q8NFG4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLCN	ENST00000285071.9	TSL:1 MANE Select	c.1579C>G	p.Arg527Gly	missense	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+1169C>G		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.1684C>G	p.Arg562Gly	missense	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Uncertain	0.080
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.49	T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D
M_CAP	Uncertain	0.23	D
MetaRNN	Uncertain	0.66	D
MetaSVM	Uncertain	0.34	D
MutationAssessor	Benign	1.5	L
PhyloP100		4.2
PrimateAI	Pathogenic	0.79	T
PROVEAN	Benign	-0.92	N
REVEL	Uncertain	0.62
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.010	D
Polyphen		0.98	D
Vest4		0.68
MutPred		0.49		Loss of MoRF binding (P = 0.0176)
MVP		0.38
MPC		1.0
ClinPred		0.91	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.54
gMVP		0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs879255683; hg19: chr17-17117130;