Variant 3-37997612-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015873.4(VILL):c.691G>T(p.Val231Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

VILL
NM_015873.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.222

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02836299).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VILL	NM_015873.4 linkuse as main transcript	c.691G>T	p.Val231Leu	missense_variant	7/20	ENST00000383759.7	NP_056957.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VILL	ENST00000383759.7 linkuse as main transcript	c.691G>T	p.Val231Leu	missense_variant	7/20	5	NM_015873.4	ENSP00000373266	P1	O15195-1
VILL	ENST00000283713.10 linkuse as main transcript	c.691G>T	p.Val231Leu	missense_variant	7/20	1		ENSP00000283713	P1	O15195-1
VILL	ENST00000484717.5 linkuse as main transcript	n.664G>T		non_coding_transcript_exon_variant	4/10	1
VILL	ENST00000465644.5 linkuse as main transcript	c.115-1318G>T		intron_variant		5		ENSP00000422096

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

250040

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.0000619

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461436

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727068

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

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

Jan 04, 2024

The c.691G>T (p.V231L) alteration is located in exon 6 (coding exon 6) of the VILL gene. This alteration results from a G to T substitution at nucleotide position 691, causing the valine (V) at amino acid position 231 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

0.12

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.9

DANN

Benign

0.92

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.59

T;.

M_CAP

Benign

0.0053

MetaRNN

Benign

0.028

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.092

Sift

Benign

0.73

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.0

B;B

Vest4

0.072

MutPred

0.45

Loss of MoRF binding (P = 0.087);Loss of MoRF binding (P = 0.087);

MVP

0.030

MPC

0.20

ClinPred

0.024

GERP RS

-0.38

Varity_R

0.030

gMVP

0.17

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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