chr17-18246396-T-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_002018.4(FLII):āc.3118A>Gā(p.Ile1040Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000582 in 1,614,064 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00036 ( 0 hom., cov: 32)
Exomes š: 0.000027 ( 0 hom. )
Consequence
FLII
NM_002018.4 missense
NM_002018.4 missense
Scores
1
5
12
Clinical Significance
Conservation
PhyloP100: 4.53
Genes affected
FLII (HGNC:3750): (FLII actin remodeling protein) This gene encodes a protein with a gelsolin-like actin binding domain and an N-terminal leucine-rich repeat-protein protein interaction domain. The protein is similar to a Drosophila protein involved in early embryogenesis and the structural organization of indirect flight muscle. The gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.06299043).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FLII | NM_002018.4 | c.3118A>G | p.Ile1040Val | missense_variant | 24/30 | ENST00000327031.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FLII | ENST00000327031.9 | c.3118A>G | p.Ile1040Val | missense_variant | 24/30 | 1 | NM_002018.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000361 AC: 55AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000836 AC: 21AN: 251324Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135898
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461736Hom.: 0 Cov.: 34 AF XY: 0.0000275 AC XY: 20AN XY: 727208
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GnomAD4 genome AF: 0.000361 AC: 55AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17AN XY: 74482
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2024 | The c.3118A>G (p.I1040V) alteration is located in exon 24 (coding exon 24) of the FLII gene. This alteration results from a A to G substitution at nucleotide position 3118, causing the isoleucine (I) at amino acid position 1040 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
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
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;.;.
REVEL
Benign
Sift
Benign
D;.;.
Sift4G
Uncertain
D;D;D
Polyphen
P;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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