rs764559568

Variant names:

• chr2-218423828-C-G
• NM_007127.3:c.50C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-218423828-C-G
• chr2-218423828-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007127.3(VIL1):​c.50C>G​(p.Pro17Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P17L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: VIL1 NM_007127.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.21

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.809

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIL1	NM_007127.3	c.50C>G	p.Pro17Arg	missense_variant	Exon 2 of 20	ENST00000248444.10	NP_009058.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIL1	ENST00000248444.10	c.50C>G	p.Pro17Arg	missense_variant	Exon 2 of 20	1	NM_007127.3	ENSP00000248444.5
VIL1	ENST00000440053.1	c.50C>G	p.Pro17Arg	missense_variant	Exon 1 of 9	1		ENSP00000409270.1
VIL1	ENST00000454069.5	c.50C>G	p.Pro17Arg	missense_variant	Exon 2 of 6	3		ENSP00000412657.1
VIL1	ENST00000392114.6	c.-184+4660C>G		intron_variant	Intron 1 of 14	2		ENSP00000375962.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461854 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.59	D;T;.
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.81	D;D;D
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.7	M;.;M
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Uncertain	0.44
Sift	Benign	0.036	D;D;D
Sift4G	Benign	0.071	T;D;T
Polyphen		1.0	D;.;.
Vest4		0.86
MutPred		0.69		Gain of MoRF binding (P = 0.002);Gain of MoRF binding (P = 0.002);Gain of MoRF binding (P = 0.002);
MVP		0.69
MPC		0.45
ClinPred		0.98	D
GERP RS		5.0
Varity_R		0.29
gMVP		0.79

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: chr2-219288551;