5-131651889-CA-C

Position:

• chr5-131651889-CA-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_133372.3(FNIP1):​c.3218delT​(p.Leu1073fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNIP1 NM_133372.3 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.29

Genes affected

FNIP1 (HGNC:29418): (folliculin interacting protein 1) This gene encodes a protein that binds to the tumor suppressor protein folliculin and to AMP-activated protein kinase (AMPK). The encoded protein participates in the regulation of cellular metabolism and nutrient sensing by modulating the AMPK and target of rapamycin signaling pathways. This gene has a closely related paralog that encodes a protein with similar binding activities. Both related proteins also associate with the molecular chaperone heat shock protein-90 (Hsp90) and negatively regulate its ATPase activity and facilitate its association with folliculin. [provided by RefSeq, Jul 2017]

ENSG00000273217 (HGNC:):

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 5-131651889-CA-C is Pathogenic according to our data. Variant chr5-131651889-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 1335872.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNIP1	NM_133372.3	c.3218delT	p.Leu1073fs	frameshift_variant	16/18	ENST00000510461.6	NP_588613.3
FNIP1	NM_001008738.3	c.3134delT	p.Leu1045fs	frameshift_variant	15/17		NP_001008738.3
FNIP1	NM_001346114.2	c.3083delT	p.Leu1028fs	frameshift_variant	15/17		NP_001333043.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNIP1	ENST00000510461.6	c.3218delT	p.Leu1073fs	frameshift_variant	16/18	1	NM_133372.3	ENSP00000421985.1
FNIP1	ENST00000307954.12	c.3083delT	p.Leu1028fs	frameshift_variant	15/17	1		ENSP00000310453.8
ENSG00000273217	ENST00000514667.1	c.220-47197delT		intron_variant		2		ENSP00000426948.1
FNIP1	ENST00000307968.11	c.3134delT	p.Leu1045fs	frameshift_variant	15/17	5		ENSP00000309266.7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency 93 and hypertrophic cardiomyopathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 24, 2022

- -

Computational scores

Source: dbNSFP v4.3

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: chr5-130987582;