3-37995812-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015873.4(VILL):​c.415C>T​(p.His139Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,552 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

VILL
NM_015873.4 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.10
Variant links:
Genes affected
VILL (HGNC:30906): (villin like) The protein encoded by this gene belongs to the villin/gelsolin family. It contains 6 gelsolin-like repeats and a headpiece domain. It may play a role in actin-bundling. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VILLNM_015873.4 linkuse as main transcriptc.415C>T p.His139Tyr missense_variant 5/20 ENST00000383759.7 NP_056957.3 O15195-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VILLENST00000383759.7 linkuse as main transcriptc.415C>T p.His139Tyr missense_variant 5/205 NM_015873.4 ENSP00000373266.2 O15195-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251450
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135902
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:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461552
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727082
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000187
Gnomad4 NFE exome
AF:
0.0000108
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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 GeneticsJan 18, 2022The c.415C>T (p.H139Y) alteration is located in exon 4 (coding exon 4) of the VILL gene. This alteration results from a C to T substitution at nucleotide position 415, causing the histidine (H) at amino acid position 139 to be replaced by a tyrosine (Y). 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
-0.015
T
BayesDel_noAF
Benign
-0.24
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T;T;T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.77
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.96
D;D;.
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.70
D;D;D
MetaSVM
Benign
-0.43
T
MutationAssessor
Pathogenic
3.5
M;.;M
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-5.3
D;D;D
REVEL
Benign
0.26
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0020
D;D;D
Polyphen
0.99
D;.;D
Vest4
0.48
MutPred
0.55
Loss of disorder (P = 0.0374);Loss of disorder (P = 0.0374);Loss of disorder (P = 0.0374);
MVP
0.46
MPC
0.79
ClinPred
0.99
D
GERP RS
4.9
Varity_R
0.81
gMVP
0.72

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.

Other links and lift over

dbSNP: rs765700258; hg19: chr3-38037303; API