rs149283777

Variant names:

• chr6-30731049-C-T
• rs149283777
• NM_005803.4:c.775G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-30731049-C-T
• chr6-30731049-C-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_005803.4(FLOT1):​c.775G>A​(p.Val259Met) variant causes a missense change. The variant allele was found at a frequency of 0.000259 in 1,611,444 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00026 (1 hom.)
• Consequence: FLOT1 NM_005803.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.02
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07183465).

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.775G>A	p.Val259Met	missense	Exon 9 of 13	NP_005794.1	Q5ST80
	FLOT1	NM_001318875.2		c.631G>A	p.Val211Met	missense	Exon 8 of 12	NP_001305804.1	O75955-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FLOT1	ENST00000376389.8	TSL:1 MANE Select	c.775G>A	p.Val259Met	missense	Exon 9 of 13	ENSP00000365569.3	O75955-1
	FLOT1	ENST00000903950.1		c.880G>A	p.Val294Met	missense	Exon 9 of 13	ENSP00000574009.1
	FLOT1	ENST00000914089.1		c.814G>A	p.Val272Met	missense	Exon 9 of 13	ENSP00000584148.1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152230 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000373 AC: 93 AN: 249126 AF XY: 0.000386

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000656

Gnomad NFE exome AF: 0.000441

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.000264 AC: 385 AN: 1459096 Hom.: 1 Cov.: 32 AF XY: 0.000264 AC XY: 192 AN XY: 725948

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.000447 AC: 20 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86244

European-Finnish (FIN) AF: 0.000531 AC: 27 AN: 50878

Middle Eastern (MID) AF: 0.00401 AC: 23 AN: 5736

European-Non Finnish (NFE) AF: 0.000242 AC: 269 AN: 1111838

Other (OTH) AF: 0.000530 AC: 32 AN: 60374

GnomAD4 genome AF: 0.000210 AC: 32 AN: 152348 Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18 AN XY: 74504

African (AFR) AF: 0.0000240 AC: 1 AN: 41584

American (AMR) AF: 0.000392 AC: 6 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10626

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68028

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.000395 Hom.: 0

Bravo AF: 0.000268

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000465 AC: 4

ExAC AF: 0.000329 AC: 40

EpiCase AF: 0.000600

EpiControl AF: 0.000593

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	Uncertain	0.44
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		6.0
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.19
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.022	D
Polyphen		0.87	P
Vest4		0.60
MVP		0.58
MPC		1.8
ClinPred		0.12	T
GERP RS		4.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.8
Varity_R		0.11
gMVP		0.73
Mutation Taster		=55/45	polymorphism

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

dbSNP: rs149283777; hg19: chr6-30698826;