chr17-17212476-AAAAAAAAAAAAAA-AAAAAAAAAAA

Variant names:

• chr17-17212476-AAAA-AAAAAAAAAA
• NM_144997.7:c.*1170_*1175dupTTTTTT

Variant summary

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

The NM_144997.7(FLCN):​c.*1170_*1175dupTTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: FLCN NM_144997.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.602
• 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.*1170_*1175dupTTTTTT		3_prime_UTR	Exon 14 of 14	NP_659434.2
	FLCN	NM_001353229.2		c.*1170_*1175dupTTTTTT		3_prime_UTR	Exon 16 of 16	NP_001340158.1
	FLCN	NM_001353230.2		c.*1170_*1175dupTTTTTT		3_prime_UTR	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.*1170_*1175dupTTTTTT		3_prime_UTR	Exon 14 of 14	ENSP00000285071.4	Q8NFG4-1
	ENSG00000264187	ENST00000427497.3	TSL:1	n.*372+2500_*372+2505dupTTTTTT		intron	N/A	ENSP00000394249.3	J3QW42
	FLCN	ENST00000962729.1		c.*1170_*1175dupTTTTTT		3_prime_UTR	Exon 16 of 16	ENSP00000632788.1

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.60

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr17-17115790;