Variant chr4-158825920-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_020840.3(FNIP2):c.112T>C(p.Ser38Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000125 in 1,605,772 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

FNIP2
NM_020840.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.849

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:

Genome browser will be placed here

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=0.07104713).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNIP2	NM_020840.3 link	c.112T>C	p.Ser38Pro	missense_variant	2/17	ENST00000264433.11	NP_065891.1	Q9P278-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FNIP2	ENST00000264433.11 link	c.112T>C	p.Ser38Pro	missense_variant	2/17	1	NM_020840.3	ENSP00000264433.6	Q9P278-1
FNIP2	ENST00000512986.5 link	c.181T>C	p.Ser61Pro	missense_variant	2/13	1		ENSP00000421488.1	D6RFH5
FNIP2	ENST00000504704.6 link	n.131T>C		non_coding_transcript_exon_variant	2/6	1
FNIP2	ENST00000505445.1 link	n.298T>C		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000562

AC:

AN:

249216

Hom.:

AF XY:

0.0000666

AC XY:

AN XY:

135202

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1453564

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

722808

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000359

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.0000331

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2021

The c.112T>C (p.S38P) alteration is located in exon 2 (coding exon 2) of the FNIP2 gene. This alteration results from a T to C substitution at nucleotide position 112, causing the serine (S) at amino acid position 38 to be replaced by a proline (P). 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

Benign

0.085

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0079

T;T

Eigen

Benign

-0.16

Eigen_PC

Benign

0.059

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.0044

MetaRNN

Benign

0.071

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.75

N;.

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

0.24

N;N

REVEL

Benign

0.055

Sift

Benign

0.50

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.084

B;B

Vest4

0.26

MutPred

0.37

Gain of catalytic residue at S38 (P = 0.0022);.;

MVP

0.043

MPC

0.19

ClinPred

0.083

GERP RS

5.8

Varity_R

0.12

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over