2-218427969-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The ENST00000248444.10(VIL1):c.352C>T(p.Arg118Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,766 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 (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )
Consequence
VIL1
ENST00000248444.10 missense
ENST00000248444.10 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 1.75
Genes affected
VIL1 (HGNC:12690): (villin 1) This gene encodes a member of a family of calcium-regulated actin-binding proteins. This protein represents a dominant part of the brush border cytoskeleton which functions in the capping, severing, and bundling of actin filaments. Two mRNAs of 2.7 kb and 3.5 kb have been observed; they result from utilization of alternate poly-adenylation signals present in the terminal exon. [provided by RefSeq, Jul 2008]
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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=0.20693973).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
VIL1 | NM_007127.3 | c.352C>T | p.Arg118Trp | missense_variant | 5/20 | ENST00000248444.10 | NP_009058.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
VIL1 | ENST00000248444.10 | c.352C>T | p.Arg118Trp | missense_variant | 5/20 | 1 | NM_007127.3 | ENSP00000248444 | P1 | |
VIL1 | ENST00000440053.1 | c.352C>T | p.Arg118Trp | missense_variant | 4/9 | 1 | ENSP00000409270 | |||
VIL1 | ENST00000454069.5 | c.340C>T | p.Arg114Trp | missense_variant | 5/6 | 3 | ENSP00000412657 | |||
VIL1 | ENST00000392114.6 | c.-183-1499C>T | intron_variant | 2 | ENSP00000375962 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152134Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000597 AC: 15AN: 251226Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135764
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GnomAD4 exome AF: 0.0000267 AC: 39AN: 1461632Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 18AN XY: 727128
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GnomAD4 genome AF: 0.0000986 AC: 15AN: 152134Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74316
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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 | Aug 23, 2021 | The c.352C>T (p.R118W) alteration is located in exon 5 (coding exon 4) of the VIL1 gene. This alteration results from a C to T substitution at nucleotide position 352, causing the arginine (R) at amino acid position 118 to be replaced by a tryptophan (W). 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
Uncertain
D;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M
MutationTaster
Benign
D;N;N
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;.
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