4-158904486-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_020840.3(FNIP2):​c.3287C>T​(p.Pro1096Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

FNIP2
NM_020840.3 missense

Scores

4
11
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.57
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]
SPMIP2 (HGNC:26342): (sperm microtubule inner protein 2)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.831

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FNIP2NM_020840.3 linkc.3287C>T p.Pro1096Leu missense_variant Exon 17 of 17 ENST00000264433.11 NP_065891.1 Q9P278-1
SPMIP2NM_152543.3 linkc.546+10684G>A intron_variant Intron 4 of 4 ENST00000434826.3 NP_689756.2 Q96LM5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FNIP2ENST00000264433.11 linkc.3287C>T p.Pro1096Leu missense_variant Exon 17 of 17 1 NM_020840.3 ENSP00000264433.6 Q9P278-1
C4orf45ENST00000434826.3 linkc.546+10684G>A intron_variant Intron 4 of 4 2 NM_152543.3 ENSP00000412215.2 Q96LM5
C4orf45ENST00000508011.1 linkn.582+10684G>A intron_variant Intron 3 of 3 3

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 24, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.3287C>T (p.P1096L) alteration is located in exon 17 (coding exon 17) of the FNIP2 gene. This alteration results from a C to T substitution at nucleotide position 3287, causing the proline (P) at amino acid position 1096 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.71
BayesDel_addAF
Uncertain
0.085
D
BayesDel_noAF
Benign
-0.12
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.40
T
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.97
D
M_CAP
Uncertain
0.13
D
MetaRNN
Pathogenic
0.83
D
MetaSVM
Benign
-0.44
T
MutationAssessor
Uncertain
2.7
M
PrimateAI
Uncertain
0.74
T
PROVEAN
Pathogenic
-7.3
D
REVEL
Uncertain
0.48
Sift
Uncertain
0.0060
D
Sift4G
Uncertain
0.026
D
Polyphen
1.0
D
Vest4
0.75
MutPred
0.55
Gain of helix (P = 0.062);
MVP
0.13
MPC
0.63
ClinPred
0.99
D
GERP RS
5.2
Varity_R
0.60
gMVP
0.80

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: chr4-159825638; API