NM_020840.3:c.395C>T

Variant names:

• chr4-158831874-C-T
• NM_020840.3:c.395C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020840.3(FNIP2):​c.395C>T​(p.Ala132Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNIP2 NM_020840.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.58
• Publications: 0 publications found

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]

ACMG classification

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=0.13036057).

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.395C>T	p.Ala132Val	missense	Exon 4 of 17	NP_065891.1	Q9P278-1
	FNIP2	NM_001366843.1		c.464C>T	p.Ala155Val	missense	Exon 4 of 18	NP_001353772.1
	FNIP2	NM_001323916.2		c.464C>T	p.Ala155Val	missense	Exon 4 of 17	NP_001310845.1	Q9P278-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FNIP2	ENST00000264433.11	TSL:1 MANE Select	c.395C>T	p.Ala132Val	missense	Exon 4 of 17	ENSP00000264433.6	Q9P278-1
	FNIP2	ENST00000512986.5	TSL:1	c.464C>T	p.Ala155Val	missense	Exon 4 of 13	ENSP00000421488.1	D6RFH5
	FNIP2	ENST00000504704.6	TSL:1	n.414C>T		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.86	D
M_CAP	Benign	0.0059	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.6
PrimateAI	Uncertain	0.50	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.12
Sift	Benign	0.055	T
Sift4G	Uncertain	0.058	T
Polyphen		0.041	B
Vest4		0.21
MutPred		0.21		Gain of glycosylation at Y128 (P = 0.0095)
MVP		0.12
MPC		0.16
ClinPred		0.96	D
GERP RS		5.1
PromoterAI		-0.031	Neutral
Varity_R		0.32
gMVP		0.56
Mutation Taster		=40/60	disease causing

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

Other links and lift over

hg19: chr4-159753026;