dbSNP rs769245388: FNIP2:p.Ala22Val (chr4-158769277-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_020840.3(FNIP2):c.65C>T(p.Ala22Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000022 in 1,542,474 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A22T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

FNIP2
NM_020840.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.462

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007119417).

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.65C>T	p.Ala22Val	missense	Exon 1 of 17	NP_065891.1	Q9P278-1
	FNIP2	NM_001346043.2		c.-796C>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.65C>T	p.Ala22Val	missense	Exon 1 of 17	ENSP00000264433.6	Q9P278-1
FNIP2	ENST00000504704.6	TSL:1	n.84C>T		non_coding_transcript_exon	Exon 1 of 6
FNIP2	ENST00000956831.1		c.65C>T	p.Ala22Val	missense	Exon 1 of 18	ENSP00000626890.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152060

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000774

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000914

AC:

AN:

142202

AF XY:

0.0000631

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000418

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00113

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000264

GnomAD4 exome

AF:

0.0000194

AC:

AN:

1390298

Hom.:

Cov.:

AF XY:

0.0000189

AC XY:

AN XY:

687758

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30360

American (AMR)

AF:

0.0000553

AC:

AN:

36194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24652

East Asian (EAS)

AF:

0.000647

AC:

AN:

34006

South Asian (SAS)

AF:

0.00

AC:

AN:

78814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4594

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1080174

Other (OTH)

AF:

0.0000520

AC:

AN:

57646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41554

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000775

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67962

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000299

Hom.:

Bravo

AF:

0.0000756

ExAC

AF:

0.0000629

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0049

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.53

M_CAP

Benign

0.067

MetaRNN

Benign

0.0071

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

0.46

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.79

REVEL

Benign

0.060

Sift

Benign

0.20

Sift4G

Benign

0.18

Polyphen

0.98

Vest4

0.14

MutPred

0.14

Gain of glycosylation at S18 (P = 0.0129)

MVP

0.068

MPC

0.32

ClinPred

0.11

GERP RS

3.0

PromoterAI

-0.0098

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.0

Varity_R

0.080

gMVP

0.093

Mutation Taster

=83/17

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over