6-30740512-C-T

Position:

• chr6-30740512-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005803.4(FLOT1):​c.554G>A​(p.Arg185Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,548 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FLOT1 NM_005803.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLOT1	NM_005803.4	c.554G>A	p.Arg185Lys	missense_variant	7/13	ENST00000376389.8	NP_005794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLOT1	ENST00000376389.8	c.554G>A	p.Arg185Lys	missense_variant	7/13	1	NM_005803.4	ENSP00000365569.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460548 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726606

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2024

The c.554G>A (p.R185K) alteration is located in exon 7 (coding exon 6) of the FLOT1 gene. This alteration results from a G to A substitution at nucleotide position 554, causing the arginine (R) at amino acid position 185 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	D;T;T;T;T;T;T
Eigen	Benign	0.040
Eigen_PC	Benign	0.19
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.076	D
MetaRNN	Uncertain	0.66	D;D;D;D;D;D;D
MetaSVM	Pathogenic	0.99	D
MutationAssessor	Benign	1.6	L;.;.;.;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.8	N;N;N;N;N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.21	T;T;T;T;T;T;T
Sift4G	Benign	0.36	T;.;.;T;T;.;.
Polyphen		0.011	B;.;.;.;.;.;.
Vest4		0.17
MutPred		0.54		Gain of ubiquitination at R185 (P = 0.0094);.;Gain of ubiquitination at R185 (P = 0.0094);.;Gain of ubiquitination at R185 (P = 0.0094);.;Gain of ubiquitination at R185 (P = 0.0094);
MVP		0.95
MPC		1.1
ClinPred		0.82	D
GERP RS		4.7
Varity_R		0.39
gMVP		0.87

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: chr6-30708289;