5-131690525-G-C

Variant names:

• chr5-131690525-G-C
• rs152815
• NM_133372.3:c.1202+8392C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133372.3(FNIP1):​c.1202+8392C>G variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FNIP1 NM_133372.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137
• Publications: 7 publications found

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]

FNIP1 Gene-Disease associations (from GenCC):

• FNIP1-associated syndrome

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• immunodeficiency 93 and hypertrophic cardiomyopathy

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000273217 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNIP1	NM_133372.3	c.1202+8392C>G		intron_variant	Intron 11 of 17	ENST00000510461.6	NP_588613.3
FNIP1	NM_001008738.3	c.1118+8392C>G		intron_variant	Intron 10 of 16		NP_001008738.3
FNIP1	NM_001346114.2	c.1067+8392C>G		intron_variant	Intron 10 of 16		NP_001333043.1
FNIP1	NM_001346113.2	c.1202+8392C>G		intron_variant	Intron 11 of 12		NP_001333042.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FNIP1	ENST00000510461.6	c.1202+8392C>G		intron_variant	Intron 11 of 17	1	NM_133372.3	ENSP00000421985.1
ENSG00000273217	ENST00000514667.1	c.219+54039C>G		intron_variant	Intron 2 of 28	2		ENSP00000426948.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 838

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.47
PhyloP100		0.14

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

Other links and lift over

dbSNP: rs152815; hg19: chr5-131026218;