rs587778371
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004119.3(FLT3):c.844G>T(p.Gly282Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,613,960 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: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
FLT3
NM_004119.3 missense
NM_004119.3 missense
Scores
6
13
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.966
Genes affected
FLT3 (HGNC:3765): (fms related receptor tyrosine kinase 3) This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia. [provided by RefSeq, Jan 2015]
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ACMG classification
Classification made for transcript
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 |
---|---|---|---|---|---|---|---|---|
FLT3 | NM_004119.3 | c.844G>T | p.Gly282Trp | missense_variant | 7/24 | ENST00000241453.12 | NP_004110.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FLT3 | ENST00000241453.12 | c.844G>T | p.Gly282Trp | missense_variant | 7/24 | 1 | NM_004119.3 | ENSP00000241453.7 | ||
FLT3 | ENST00000380987.2 | n.844G>T | non_coding_transcript_exon_variant | 7/25 | 1 | ENSP00000370374.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461834Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727216
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152126Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74298
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ClinVar
Not reported inComputational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of catalytic residue at L283 (P = 0);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at