2-218428237-C-T

Variant names:

• chr2-218428237-C-T
• rs1038856514
• NM_007127.3:c.467C>T

Variant summary

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

The NM_007127.3(VIL1):​c.467C>T​(p.Ser156Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: VIL1 NM_007127.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.31

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]

ACMG classification

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 rank	MANE	Protein	UniProt
VIL1	NM_007127.3	c.467C>T	p.Ser156Phe	missense_variant	Exon 6 of 20	ENST00000248444.10	NP_009058.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIL1	ENST00000248444.10	c.467C>T	p.Ser156Phe	missense_variant	Exon 6 of 20	1	NM_007127.3	ENSP00000248444.5
VIL1	ENST00000440053.1	c.467C>T	p.Ser156Phe	missense_variant	Exon 5 of 9	1		ENSP00000409270.1
VIL1	ENST00000454069.5	c.455C>T	p.Ser152Phe	missense_variant	Exon 6 of 6	3		ENSP00000412657.1
VIL1	ENST00000392114.6	c.-183-1231C>T		intron_variant	Intron 1 of 14	2		ENSP00000375962.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461870 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 727236

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: 8.99e-7

Gnomad4 OTH exome AF: 0.0000662

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.467C>T (p.S156F) alteration is located in exon 6 (coding exon 5) of the VIL1 gene. This alteration results from a C to T substitution at nucleotide position 467, causing the serine (S) at amino acid position 156 to be replaced by a phenylalanine (F). 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	Uncertain	0.34
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	T;T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.94	D;D;D
M_CAP	Benign	0.072	D
MetaRNN	Uncertain	0.74	D;D;D
MetaSVM	Uncertain	-0.016	T
MutationAssessor	Pathogenic	3.1	M;.;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Pathogenic	-5.0	D;D;D
REVEL	Uncertain	0.31
Sift	Pathogenic	0.0	D;D;D
Sift4G	Pathogenic	0.0010	D;D;D
Polyphen		0.71	P;.;.
Vest4		0.84
MutPred		0.68		Loss of ubiquitination at K158 (P = 0.0506);.;Loss of ubiquitination at K158 (P = 0.0506);
MVP		0.91
MPC		0.62
ClinPred		0.99	D
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.52
gMVP		0.58

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

Other links and lift over

dbSNP: rs1038856514; hg19: chr2-219292960;