2-218425711-A-G

Variant summary

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

The NM_007127.3(VIL1):ā€‹c.247A>Gā€‹(p.Thr83Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

VIL1
NM_007127.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.47
Variant links:
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=0.26093036).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VIL1NM_007127.3 linkuse as main transcriptc.247A>G p.Thr83Ala missense_variant 4/20 ENST00000248444.10 NP_009058.2 P09327-1Q53F91

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VIL1ENST00000248444.10 linkuse as main transcriptc.247A>G p.Thr83Ala missense_variant 4/201 NM_007127.3 ENSP00000248444.5 P09327-1
VIL1ENST00000440053.1 linkuse as main transcriptc.247A>G p.Thr83Ala missense_variant 3/91 ENSP00000409270.1 P09327-2
VIL1ENST00000454069.5 linkuse as main transcriptc.247A>G p.Thr83Ala missense_variant 4/63 ENSP00000412657.1 C9J2B5
VIL1ENST00000392114.6 linkuse as main transcriptc.-183-3757A>G intron_variant 2 ENSP00000375962.2 B4DV78

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152120
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152120
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsSep 10, 2024The c.247A>G (p.T83A) alteration is located in exon 4 (coding exon 3) of the VIL1 gene. This alteration results from a A to G substitution at nucleotide position 247, causing the threonine (T) at amino acid position 83 to be replaced by an alanine (A). 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
0.11
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
DANN
Uncertain
0.98
DEOGEN2
Benign
0.18
T;T;.
Eigen
Benign
-0.013
Eigen_PC
Benign
0.097
FATHMM_MKL
Uncertain
0.89
D
LIST_S2
Benign
0.80
T;T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.26
T;T;T
MetaSVM
Benign
-0.90
T
MutationAssessor
Benign
1.5
L;.;L
PrimateAI
Uncertain
0.64
T
PROVEAN
Benign
-1.7
N;N;N
REVEL
Benign
0.076
Sift
Benign
0.14
T;D;T
Sift4G
Benign
0.27
T;T;T
Polyphen
0.43
B;.;.
Vest4
0.41
MutPred
0.56
Loss of stability (P = 0.093);Loss of stability (P = 0.093);Loss of stability (P = 0.093);
MVP
0.66
MPC
0.25
ClinPred
0.65
D
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.14
gMVP
0.66

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs773804697; hg19: chr2-219290434; API