5-131647159-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3 PP5

The NM_133372.3(FNIP1):c.3353G>A(p.Ser1118Asn) 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 Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FNIP1 NM_133372.3 missense
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.91

Genes affected

FNIP1 (HGNC:29418): (folliculin interacting protein 1) This gene encodes a protein that binds to the tumor suppressor protein folliculin and to AMP-activated protein kinase (AMPK). The encoded protein participates in the regulation of cellular metabolism and nutrient sensing by modulating the AMPK and target of rapamycin signaling pathways. 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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811
• PP5: Variant 5-131647159-C-T is Pathogenic according to our data. Variant chr5-131647159-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1335870.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FNIP1	NM_133372.3	c.3353G>A	p.Ser1118Asn	missense_variant	17/18	ENST00000510461.6
FNIP1	NM_001008738.3	c.3269G>A	p.Ser1090Asn	missense_variant	16/17
FNIP1	NM_001346114.2	c.3218G>A	p.Ser1073Asn	missense_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FNIP1	ENST00000510461.6	c.3353G>A	p.Ser1118Asn	missense_variant	17/18	1	NM_133372.3	P4
FNIP1	ENST00000307954.12	c.3218G>A	p.Ser1073Asn	missense_variant	16/17	1
FNIP1	ENST00000307968.11	c.3269G>A	p.Ser1090Asn	missense_variant	16/17	5		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Immunodeficiency 93 and hypertrophic cardiomyopathy Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Jan 24, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Uncertain	0.031	T
BayesDel_noAF	Benign	-0.19
Cadd	Pathogenic	27
Dann	Uncertain	1.0
Eigen	Pathogenic	0.88
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.93	D;D;D;D
M_CAP	Benign	0.080	D
MetaRNN	Pathogenic	0.81	D;D;D;D
MetaSVM	Benign	-0.52	T
MutationTaster	Benign	1.0	D;D;D;D
PROVEAN	Uncertain	-2.6	D;D;.;D
REVEL	Benign	0.28
Sift	Pathogenic	0.0	D;D;.;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;.;.;D
Vest4		0.97
MutPred		0.43		.;.;.;Loss of catalytic residue at K1119 (P = 0.0433);
MVP		0.25
MPC		2.4
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.60
gMVP		0.86

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: chr5-130982852;