10-17229504-C-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003380.5(VIM):ā€‹c.82C>Gā€‹(p.Arg28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000824 in 1,455,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000082 ( 0 hom. )

Consequence

VIM
NM_003380.5 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.235
Variant links:
Genes affected
VIM (HGNC:12692): (vimentin) This gene encodes a type III intermediate filament protein. Intermediate filaments, along with microtubules and actin microfilaments, make up the cytoskeleton. The encoded protein is responsible for maintaining cell shape and integrity of the cytoplasm, and stabilizing cytoskeletal interactions. This protein is involved in neuritogenesis and cholesterol transport and functions as an organizer of a number of other critical proteins involved in cell attachment, migration, and signaling. Bacterial and viral pathogens have been shown to attach to this protein on the host cell surface. Mutations in this gene are associated with congenital cataracts in human patients. [provided by RefSeq, Aug 2017]
VIM-AS1 (HGNC:44879): (VIM antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.17952159).
BS2
High AC in GnomAdExome4 at 12 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VIMNM_003380.5 linkuse as main transcriptc.82C>G p.Arg28Gly missense_variant 2/10 ENST00000544301.7 NP_003371.2
VIM-AS1NR_108061.1 linkuse as main transcriptn.482G>C non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VIMENST00000544301.7 linkuse as main transcriptc.82C>G p.Arg28Gly missense_variant 2/101 NM_003380.5 ENSP00000446007 P1
VIM-AS1ENST00000605833.2 linkuse as main transcriptn.515G>C non_coding_transcript_exon_variant 1/33

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000824
AC:
12
AN:
1455760
Hom.:
0
Cov.:
33
AF XY:
0.00000828
AC XY:
6
AN XY:
724322
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:
0.00000720
Gnomad4 OTH exome
AF:
0.0000666
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Cataract 30 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 08, 2022Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has not been reported in the literature in individuals affected with VIM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 28 of the VIM protein (p.Arg28Gly). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
0.0057
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
19
DANN
Benign
0.70
DEOGEN2
Uncertain
0.59
D;.;.;D
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.76
FATHMM_MKL
Benign
0.081
N
LIST_S2
Benign
0.75
.;T;T;T
M_CAP
Pathogenic
0.67
D
MetaRNN
Benign
0.18
T;T;T;T
MetaSVM
Benign
-0.73
T
MutationAssessor
Benign
0.63
N;.;.;N
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.66
T
PROVEAN
Benign
-1.4
N;.;.;N
REVEL
Benign
0.28
Sift
Benign
0.12
T;.;.;T
Sift4G
Benign
0.22
T;.;.;T
Polyphen
0.0
B;.;.;B
Vest4
0.32
MutPred
0.37
Loss of methylation at R28 (P = 0.0276);Loss of methylation at R28 (P = 0.0276);Loss of methylation at R28 (P = 0.0276);Loss of methylation at R28 (P = 0.0276);
MVP
0.29
MPC
0.66
ClinPred
0.075
T
GERP RS
4.5
Varity_R
0.15

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: chr10-17271503; API