Variant 2-218423828-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_007127.3(VIL1):c.50C>T(p.Pro17Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000142 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

VIL1
NM_007127.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.21

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]

VIL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIL1	NM_007127.3 linkuse as main transcript	c.50C>T	p.Pro17Leu	missense_variant	2/20	ENST00000248444.10	NP_009058.2	P09327-1Q53F91

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VIL1	ENST00000248444.10 linkuse as main transcript	c.50C>T	p.Pro17Leu	missense_variant	2/20	1	NM_007127.3	ENSP00000248444.5	P09327-1
VIL1	ENST00000440053.1 linkuse as main transcript	c.50C>T	p.Pro17Leu	missense_variant	1/9	1		ENSP00000409270.1	P09327-2
VIL1	ENST00000454069.5 linkuse as main transcript	c.50C>T	p.Pro17Leu	missense_variant	2/6	3		ENSP00000412657.1	C9J2B5
VIL1	ENST00000392114.6 linkuse as main transcript	c.-184+4660C>T		intron_variant		2		ENSP00000375962.2	B4DV78

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251312

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461854

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152186

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

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:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000540

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 20, 2024

The c.50C>T (p.P17L) alteration is located in exon 2 (coding exon 1) of the VIL1 gene. This alteration results from a C to T substitution at nucleotide position 50, causing the proline (P) at amino acid position 17 to be replaced by a leucine (L). 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

0.15

BayesDel_addAF

Benign

0.0033

BayesDel_noAF

Uncertain

-0.010

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.65

D;T;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.099

MetaRNN

Pathogenic

0.78

D;D;D

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.9

M;.;M

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-4.3

D;D;D

REVEL

Uncertain

0.42

Sift

Uncertain

0.0010

D;D;D

Sift4G

Uncertain

0.0070

D;T;T

Polyphen

1.0

D;.;.

Vest4

0.77

MutPred

0.64

Gain of MoRF binding (P = 0.0668);Gain of MoRF binding (P = 0.0668);Gain of MoRF binding (P = 0.0668);

MVP

0.66

MPC

0.69

ClinPred

0.92

GERP RS

5.0

Varity_R

0.34

gMVP

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over