2-218428002-G-A

Variant summary

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

The NM_007127.3(VIL1):​c.385G>A​(p.Val129Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

VIL1
NM_007127.3 missense

Scores

3
8
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.03
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]

Genome browser will be placed here

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=0.22072273).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VIL1NM_007127.3 linkuse as main transcriptc.385G>A p.Val129Met missense_variant 5/20 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.385G>A p.Val129Met missense_variant 5/201 NM_007127.3 ENSP00000248444.5 P09327-1
VIL1ENST00000440053.1 linkuse as main transcriptc.385G>A p.Val129Met missense_variant 4/91 ENSP00000409270.1 P09327-2
VIL1ENST00000454069.5 linkuse as main transcriptc.373G>A p.Val125Met missense_variant 5/63 ENSP00000412657.1 C9J2B5
VIL1ENST00000392114.6 linkuse as main transcriptc.-183-1466G>A intron_variant 2 ENSP00000375962.2 B4DV78

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152176
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00548
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251426
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461870
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000162
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152176
Hom.:
0
Cov.:
31
AF XY:
0.0000807
AC XY:
6
AN XY:
74340
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000386
Hom.:
0
Bravo
AF:
0.000117
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
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 GeneticsNov 08, 2024The c.385G>A (p.V129M) alteration is located in exon 5 (coding exon 4) of the VIL1 gene. This alteration results from a G to A substitution at nucleotide position 385, causing the valine (V) at amino acid position 129 to be replaced by a methionine (M). 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
0.14
BayesDel_addAF
Benign
-0.068
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.80
D;T;.
Eigen
Uncertain
0.34
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.96
D;D;D
M_CAP
Benign
0.039
D
MetaRNN
Benign
0.22
T;T;T
MetaSVM
Benign
-0.78
T
MutationAssessor
Pathogenic
3.3
M;.;M
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-2.6
D;D;D
REVEL
Benign
0.21
Sift
Uncertain
0.0060
D;D;D
Sift4G
Pathogenic
0.0010
D;D;D
Polyphen
0.98
D;.;.
Vest4
0.35
MVP
0.63
MPC
0.36
ClinPred
0.93
D
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.27
gMVP
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs374719806; hg19: chr2-219292725; COSMIC: COSV50286716; COSMIC: COSV50286716; API