Genetic Variant NM_020840.3:c.25C>T (chr4-158769237-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020840.3(FNIP2):c.25C>T(p.Leu9Phe) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L9V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FNIP2
NM_020840.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.38

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25262722).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020840.3. 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
	FNIP2	NM_020840.3	MANE Select	c.25C>T	p.Leu9Phe	missense	Exon 1 of 17	NP_065891.1	Q9P278-1
	FNIP2	NM_001346043.2		c.-836C>T		5_prime_UTR	Exon 1 of 16	NP_001332972.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FNIP2	ENST00000264433.11	TSL:1 MANE Select	c.25C>T	p.Leu9Phe	missense	Exon 1 of 17	ENSP00000264433.6	Q9P278-1
FNIP2	ENST00000504704.6	TSL:1	n.44C>T		non_coding_transcript_exon	Exon 1 of 6
FNIP2	ENST00000956831.1		c.25C>T	p.Leu9Phe	missense	Exon 1 of 18	ENSP00000626890.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1375710

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

680730

African (AFR)

AF:

0.00

AC:

AN:

29438

American (AMR)

AF:

0.00

AC:

AN:

35382

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24278

East Asian (EAS)

AF:

0.00

AC:

AN:

32492

South Asian (SAS)

AF:

0.00

AC:

AN:

78140

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41432

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4222

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073478

Other (OTH)

AF:

0.00

AC:

AN:

56848

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.72

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.23

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

PhyloP100

3.4

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.9

REVEL

Benign

0.11

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.029

Polyphen

1.0

Vest4

0.36

MutPred

0.17

Gain of glycosylation at T4 (P = 0.0792)

MVP

0.10

MPC

0.65

ClinPred

0.92

GERP RS

2.0

PromoterAI

-0.033

Neutral

(source)

Varity_R

0.17

gMVP

0.23

Mutation Taster

=67/33

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over