rs764559568

Variant summary

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

The NM_007127.3(VIL1):​c.50C>G​(p.Pro17Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,854 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

VIL1
NM_007127.3 missense

Scores

3
10
6

Clinical Significance

Not reported in ClinVar

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]

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, 0.809

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VIL1NM_007127.3 linkc.50C>G p.Pro17Arg missense_variant Exon 2 of 20 ENST00000248444.10 NP_009058.2 P09327-1Q53F91

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VIL1ENST00000248444.10 linkc.50C>G p.Pro17Arg missense_variant Exon 2 of 20 1 NM_007127.3 ENSP00000248444.5 P09327-1
VIL1ENST00000440053.1 linkc.50C>G p.Pro17Arg missense_variant Exon 1 of 9 1 ENSP00000409270.1 P09327-2
VIL1ENST00000454069.5 linkc.50C>G p.Pro17Arg missense_variant Exon 2 of 6 3 ENSP00000412657.1 C9J2B5
VIL1ENST00000392114.6 linkc.-184+4660C>G intron_variant Intron 1 of 14 2 ENSP00000375962.2 B4DV78

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461854
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727234
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.18
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.060
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.59
D;T;.
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.47
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.91
D;D;D
M_CAP
Benign
0.047
D
MetaRNN
Pathogenic
0.81
D;D;D
MetaSVM
Benign
-0.93
T
MutationAssessor
Uncertain
2.7
M;.;M
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-2.8
D;D;D
REVEL
Uncertain
0.44
Sift
Benign
0.036
D;D;D
Sift4G
Benign
0.071
T;D;T
Polyphen
1.0
D;.;.
Vest4
0.86
MutPred
0.69
Gain of MoRF binding (P = 0.002);Gain of MoRF binding (P = 0.002);Gain of MoRF binding (P = 0.002);
MVP
0.69
MPC
0.45
ClinPred
0.98
D
GERP RS
5.0
Varity_R
0.29
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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219288551; API