dbSNP rs891200138: FLOT1:p.Glu288Lys (chr6-30730962-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_005803.4(FLOT1):c.862G>A(p.Glu288Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

FLOT1
NM_005803.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.03

Publications

0 publications found

Variant links:

Genes affected

FLOT1 (HGNC:3757): (flotillin 1) This gene encodes an protein that localizes to the caveolae, which are small domains on the inner cell membranes. This protein plays a role in vesicle trafficking and cell morphology. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

FLOT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005803.4. 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
	FLOT1	NM_005803.4	MANE Select	c.862G>A	p.Glu288Lys	missense	Exon 9 of 13	NP_005794.1	Q5ST80
	FLOT1	NM_001318875.2		c.718G>A	p.Glu240Lys	missense	Exon 8 of 12	NP_001305804.1	O75955-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FLOT1	ENST00000376389.8	TSL:1 MANE Select	c.862G>A	p.Glu288Lys	missense	Exon 9 of 13	ENSP00000365569.3	O75955-1
FLOT1	ENST00000903950.1		c.967G>A	p.Glu323Lys	missense	Exon 9 of 13	ENSP00000574009.1
FLOT1	ENST00000914089.1		c.901G>A	p.Glu301Lys	missense	Exon 9 of 13	ENSP00000584148.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152222

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461640

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53318

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111934

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41464

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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:

0.00

Hom.:

Bravo

AF:

0.00000756

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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

Eigen

Benign

0.061

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.022

MetaRNN

Uncertain

0.46

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.8

PhyloP100

6.0

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.25

Sift

Benign

0.039

Sift4G

Uncertain

0.040

Polyphen

0.0010

Vest4

0.64

MutPred

0.41

Gain of MoRF binding (P = 0.0161)

MVP

0.56

MPC

1.1

ClinPred

0.98

GERP RS

4.7

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.44

gMVP

0.80

Mutation Taster

=29/71

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over