6-30740247-C-A

Position:

• chr6-30740247-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005803.4(FLOT1):​c.634G>T​(p.Ala212Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: FLOT1 NM_005803.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.57

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22000578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLOT1	NM_005803.4	c.634G>T	p.Ala212Ser	missense_variant	8/13	ENST00000376389.8	NP_005794.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FLOT1	ENST00000376389.8	c.634G>T	p.Ala212Ser	missense_variant	8/13	1	NM_005803.4	ENSP00000365569.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Jul 26, 2022

The c.634G>T (p.A212S) alteration is located in exon 8 (coding exon 7) of the FLOT1 gene. This alteration results from a G to T substitution at nucleotide position 634, causing the alanine (A) at amino acid position 212 to be replaced by a serine (S). 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	0.078
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	24
DANN	Benign	0.92
DEOGEN2	Benign	0.20	T;T;T;T;T
Eigen	Benign	-0.092
Eigen_PC	Benign	0.048
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.22	T;T;T;T;T
MetaSVM	Uncertain	-0.079	T
MutationAssessor	Benign	1.4	L;.;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.15	N;N;N;N;N
REVEL	Benign	0.076
Sift	Benign	0.68	T;T;T;T;T
Sift4G	Benign	0.44	T;.;.;T;T
Polyphen		0.30	B;.;.;.;.
Vest4		0.17
MutPred		0.43		Gain of phosphorylation at A212 (P = 0.0298);.;Gain of phosphorylation at A212 (P = 0.0298);.;Gain of phosphorylation at A212 (P = 0.0298);
MVP		0.87
MPC		1.0
ClinPred		0.85	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.67

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: chr6-30708024;