chr4-158895783-A-G

Position:

chr4-158895783-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000264433.11(FNIP2):c.3184A>G(p.Met1062Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,612,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

FNIP2
ENST00000264433.11 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.20

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:

C4orf45 (HGNC:):

C4orf45 links:

SPMIP2 (HGNC:26342): (sperm microtubule inner protein 2)

SPMIP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021826178).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FNIP2	NM_020840.3 linkuse as main transcript	c.3184A>G	p.Met1062Val	missense_variant	16/17	ENST00000264433.11	NP_065891.1
C4orf45	NM_152543.3 linkuse as main transcript	c.547-2066T>C		intron_variant		ENST00000434826.3	NP_689756.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FNIP2	ENST00000264433.11 linkuse as main transcript	c.3184A>G	p.Met1062Val	missense_variant	16/17	1	NM_020840.3	ENSP00000264433	P1	Q9P278-1
SPMIP2	ENST00000434826.3 linkuse as main transcript	c.547-2066T>C		intron_variant		2	NM_152543.3	ENSP00000412215	P1
SPMIP2	ENST00000508011.1 linkuse as main transcript	n.583-2066T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000178

AC:

AN:

247874

Hom.:

AF XY:

0.000216

AC XY:

AN XY:

134400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000292

Gnomad ASJ exome

AF:

0.00389

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000787

AC:

115

AN:

1460616

Hom.:

Cov.:

AF XY:

0.0000812

AC XY:

AN XY:

726498

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000898

Gnomad4 ASJ exome

AF:

0.00307

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000117

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.000102

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000121

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.0000546

EpiControl

AF:

0.00

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

Apr 25, 2022

The c.3184A>G (p.M1062V) alteration is located in exon 16 (coding exon 16) of the FNIP2 gene. This alteration results from a A to G substitution at nucleotide position 3184, causing the methionine (M) at amino acid position 1062 to be replaced by a valine (V). 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

0.21

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.015

Eigen

Benign

-0.10

Eigen_PC

Benign

-0.027

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.70

M_CAP

Benign

0.013

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.29

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-0.97

REVEL

Benign

0.11

Sift

Benign

0.074

Sift4G

Benign

0.31

Polyphen

0.45

Vest4

0.24

MVP

0.043

MPC

0.16

ClinPred

0.046

GERP RS

2.9

Varity_R

0.23

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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