6-30730705-C-T

Variant names:

• chr6-30730705-C-T
• rs1777113204
• NM_005803.4:c.928G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_005803.4(FLOT1):​c.928G>A​(p.Glu310Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,028 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FLOT1 NM_005803.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.85
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41306624).

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.928G>A	p.Glu310Lys	missense	Exon 10 of 13	NP_005794.1	Q5ST80
	FLOT1	NM_001318875.2		c.784G>A	p.Glu262Lys	missense	Exon 9 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.928G>A	p.Glu310Lys	missense	Exon 10 of 13	ENSP00000365569.3	O75955-1
	FLOT1	ENST00000903950.1		c.1033G>A	p.Glu345Lys	missense	Exon 10 of 13	ENSP00000574009.1
	FLOT1	ENST00000914089.1		c.967G>A	p.Glu323Lys	missense	Exon 10 of 13	ENSP00000584148.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461028 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726824

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112006

Other (OTH) AF: 0.00 AC: 0 AN: 60384

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.23
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.60	D
Eigen	Uncertain	0.51
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Uncertain	0.095	D
MetaRNN	Benign	0.41	T
MetaSVM	Uncertain	0.73	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.8
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.53
Sift	Benign	0.23	T
Sift4G	Uncertain	0.029	D
Polyphen		0.98	D
Vest4		0.32
MutPred		0.40		Gain of MoRF binding (P = 7e-04)
MVP		0.97
MPC		2.2
ClinPred		0.99	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.84
Mutation Taster		=22/78	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

dbSNP: rs1777113204; hg19: chr6-30698482;