6-30741645-C-A

Position:

• chr6-30741645-C-A

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_005803.4(FLOT1):​c.179G>T​(p.Gly60Val) 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FLOT1 NM_005803.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.38

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.955

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLOT1	NM_005803.4	c.179G>T	p.Gly60Val	missense_variant	4/13	ENST00000376389.8	NP_005794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLOT1	ENST00000376389.8	c.179G>T	p.Gly60Val	missense_variant	4/13	1	NM_005803.4	ENSP00000365569.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Oct 25, 2023

The c.179G>T (p.G60V) alteration is located in exon 4 (coding exon 3) of the FLOT1 gene. This alteration results from a G to T substitution at nucleotide position 179, causing the glycine (G) at amino acid position 60 to be replaced by a valine (V). 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	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.96	D;D;D;D
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.84
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Pathogenic	0.95	D;D;D;D
MetaSVM	Uncertain	0.30	D
MutationAssessor	Pathogenic	3.7	H;.;.;.
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-8.6	D;D;D;D
REVEL	Pathogenic	0.66
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;.;D;.
Polyphen		1.0	D;.;.;.
Vest4		0.82
MutPred		0.82		Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);Gain of sheet (P = 0.0344);
MVP		0.94
MPC		2.4
ClinPred		1.0	D
GERP RS		4.9
Varity_R		0.92
gMVP		0.97

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: chr6-30709422;