Variant 3-37993949-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_015873.4(VILL):c.112G>A(p.Glu38Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000101 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

VILL
NM_015873.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.85

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]

VILL links:

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
VILL	NM_015873.4 linkuse as main transcript	c.112G>A	p.Glu38Lys	missense_variant	3/20	ENST00000383759.7	NP_056957.3
VILL	NM_001385038.1 linkuse as main transcript	c.112G>A	p.Glu38Lys	missense_variant	4/21		NP_001371967.1
VILL	NM_001385039.1 linkuse as main transcript	c.112G>A	p.Glu38Lys	missense_variant	3/20		NP_001371968.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VILL	ENST00000383759.7 linkuse as main transcript	c.112G>A	p.Glu38Lys	missense_variant	3/20	5	NM_015873.4	ENSP00000373266	P1	O15195-1
VILL	ENST00000283713.10 linkuse as main transcript	c.112G>A	p.Glu38Lys	missense_variant	3/20	1		ENSP00000283713	P1	O15195-1
VILL	ENST00000492491.6 linkuse as main transcript	c.112G>A	p.Glu38Lys	missense_variant	3/6	5		ENSP00000427355
VILL	ENST00000460040.1 linkuse as main transcript	n.392G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251492

Hom.:

AF XY:

0.0000441

AC XY:

AN XY:

135920

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:

0.0000703

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000107

AC:

156

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000853

AC XY:

AN XY:

727248

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.000281

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152144

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.0000882

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

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

Aug 12, 2021

The c.112G>A (p.E38K) alteration is located in exon 2 (coding exon 2) of the VILL gene. This alteration results from a G to A substitution at nucleotide position 112, causing the glutamic acid (E) at amino acid position 38 to be replaced by a lysine (K). 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

0.092

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.059

T;.;T;T

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.42

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

T;D;T;.

M_CAP

Benign

0.023

MetaRNN

Uncertain

0.74

D;D;D;D

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.86

L;.;.;L

MutationTaster

Benign

0.52

D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.43

N;N;N;N

REVEL

Benign

0.19

Sift

Benign

0.061

T;D;D;T

Sift4G

Uncertain

0.039

D;T;T;D

Polyphen

0.0020

B;.;.;B

Vest4

0.26

MutPred

0.84

Gain of methylation at E38 (P = 0.0055);Gain of methylation at E38 (P = 0.0055);Gain of methylation at E38 (P = 0.0055);Gain of methylation at E38 (P = 0.0055);

MVP

0.20

MPC

0.24

ClinPred

0.56

GERP RS

1.5

Varity_R

0.17

gMVP

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.17

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