17-17228025-C-G

Variant names:

• chr17-17228025-C-G
• NM_144997.7:c.113G>C

Variant summary

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

The NM_144997.7(FLCN):​c.113G>C​(p.Ser38Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: FLCN NM_144997.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.61

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=0.099033386).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FLCN	NM_144997.7	c.113G>C	p.Ser38Thr	missense_variant	Exon 4 of 14	ENST00000285071.9	NP_659434.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FLCN	ENST00000285071.9	c.113G>C	p.Ser38Thr	missense_variant	Exon 4 of 14	1	NM_144997.7	ENSP00000285071.4
ENSG00000264187	ENST00000427497.3	n.113G>C		non_coding_transcript_exon_variant	Exon 4 of 12	1		ENSP00000394249.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Birt-Hogg-Dube syndrome Uncertain:1

May 13, 2023

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	14
DANN	Benign	0.83
DEOGEN2	Benign	0.13	T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.030
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.65	T;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.099	T;T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	0.97	L;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.070	N;N
REVEL	Benign	0.28
Sift	Benign	0.55	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.0020	B;B
Vest4		0.16
MutPred		0.26		Gain of glycosylation at S38 (P = 0.0694);Gain of glycosylation at S38 (P = 0.0694);
MVP		0.52
MPC		0.34
ClinPred		0.35	T
GERP RS		5.5
Varity_R		0.070
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: chr17-17131339;