6-30730921-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005803.4(FLOT1):​c.903G>C​(p.Glu301Asp) variant causes a missense, splice region 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. 15/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

FLOT1
NM_005803.4 missense, splice_region

Scores

3
15
Splicing: ADA: 0.1120
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.98
Variant links:
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]

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ACMG classification

Classification made for transcript

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=0.22562078).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FLOT1NM_005803.4 linkc.903G>C p.Glu301Asp missense_variant, splice_region_variant Exon 9 of 13 ENST00000376389.8 NP_005794.1 O75955-1Q5ST80

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FLOT1ENST00000376389.8 linkc.903G>C p.Glu301Asp missense_variant, splice_region_variant Exon 9 of 13 1 NM_005803.4 ENSP00000365569.3 O75955-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000194
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.50
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.21
T;T
Eigen
Benign
-0.13
Eigen_PC
Benign
0.027
FATHMM_MKL
Uncertain
0.89
D
M_CAP
Benign
0.0060
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L;.
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.75
N;N
REVEL
Benign
0.040
Sift
Benign
0.13
T;T
Sift4G
Benign
0.086
T;.
Polyphen
0.0010
B;.
Vest4
0.37
MutPred
0.26
Gain of MoRF binding (P = 0.0654);.;
MVP
0.46
MPC
0.93
ClinPred
0.61
D
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.23
gMVP
0.56

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.11
dbscSNV1_RF
Benign
0.31
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs138717826; hg19: chr6-30698698; API