dbSNP rs1194280553: FNIP2:p.Ile313Leu (chr4-158859136-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020840.3(FNIP2):c.937A>C(p.Ile313Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict 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: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FNIP2
NM_020840.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.20

Variant links:

Genes affected

FNIP2 (HGNC:29280): (folliculin interacting protein 2) This gene encodes a protein that binds to the tumor suppressor folliculin and to AMP-activated protein kinase (AMPK), and may play a role cellular metabolism and nutrient sensing by regulating the AMPK-mechanistic target of rapamycin signaling pathway. The encoded protein may also be involved in regulating the O6-methylguanine-induced apoptosis signaling pathway. 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]

FNIP2 links:

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ACMG classification

Classification made for transcript

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=0.21364683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FNIP2	NM_020840.3 link	c.937A>C	p.Ile313Leu	missense_variant	Exon 9 of 17	ENST00000264433.11	NP_065891.1	Q9P278-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FNIP2	ENST00000264433.11 link	c.937A>C	p.Ile313Leu	missense_variant	Exon 9 of 17	1	NM_020840.3	ENSP00000264433.6	Q9P278-1
FNIP2	ENST00000512986.5 link	c.1006A>C	p.Ile336Leu	missense_variant	Exon 9 of 13	1		ENSP00000421488.1	D6RFH5
FNIP2	ENST00000504715.1 link	c.532A>C	p.Ile178Leu	missense_variant	Exon 6 of 7	5		ENSP00000420841.1	H0Y8F3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461652

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727096

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.023

T;T;.

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Benign

0.010

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;.;.

PrimateAI

Benign

0.44

PROVEAN

Benign

-1.5

N;N;N

REVEL

Benign

0.047

Sift

Benign

0.14

T;T;T

Sift4G

Benign

0.11

T;D;D

Polyphen

0.19

B;.;.

Vest4

0.35

MutPred

0.68

Loss of sheet (P = 0.0457);.;.;

MVP

0.043

MPC

0.18

ClinPred

0.40

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.26

gMVP

0.72

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over