chr2-218423792-G-T

Position:

• chr2-218423792-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007127.3(VIL1):​c.14G>T​(p.Ser5Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: VIL1 NM_007127.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.213

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07910296).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIL1	NM_007127.3	c.14G>T	p.Ser5Ile	missense_variant	2/20	ENST00000248444.10	NP_009058.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIL1	ENST00000248444.10	c.14G>T	p.Ser5Ile	missense_variant	2/20	1	NM_007127.3	ENSP00000248444	P1
VIL1	ENST00000440053.1	c.14G>T	p.Ser5Ile	missense_variant	1/9	1		ENSP00000409270
VIL1	ENST00000454069.5	c.14G>T	p.Ser5Ile	missense_variant	2/6	3		ENSP00000412657
VIL1	ENST00000392114.6	c.-184+4624G>T		intron_variant		2		ENSP00000375962

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 10, 2023

The c.14G>T (p.S5I) alteration is located in exon 2 (coding exon 1) of the VIL1 gene. This alteration results from a G to T substitution at nucleotide position 14, causing the serine (S) at amino acid position 5 to be replaced by an isoleucine (I). 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	0.24
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T;T;.
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.78
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.70	T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.079	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	2.0	M;.;M
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-0.080	N;N;N
REVEL	Benign	0.027
Sift	Uncertain	0.0080	D;D;D
Sift4G	Uncertain	0.040	D;T;D
Polyphen		0.15	B;.;.
Vest4		0.40
MutPred		0.40		Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);Gain of helix (P = 0.0078);
MVP		0.38
MPC		0.25
ClinPred		0.17	T
GERP RS		-0.45
Varity_R		0.079
gMVP		0.64

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: chr2-219288515;