rs779204525

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The NM_003380.5(VIM):​c.23C>G​(p.Ser8Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,142 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. S8L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

VIM
NM_003380.5 missense

Scores

3
12
4

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.866
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 Uncertain_significance. Variant got 4 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity VIME_HUMAN
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
VIMNM_003380.5 linkc.23C>G p.Ser8Trp missense_variant Exon 2 of 10 ENST00000544301.7 NP_003371.2 P08670V9HWE1
VIM-AS1NR_108061.1 linkn.541G>C non_coding_transcript_exon_variant Exon 1 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
VIMENST00000544301.7 linkc.23C>G p.Ser8Trp missense_variant Exon 2 of 10 1 NM_003380.5 ENSP00000446007.1 P08670

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000435
AC:
1
AN:
230086
Hom.:
0
AF XY:
0.00000789
AC XY:
1
AN XY:
126780
show subpopulations
Gnomad AFR exome
AF:
0.00
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:
0.00000988
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.88e-7
AC:
1
AN:
1454142
Hom.:
0
Cov.:
33
AF XY:
0.00000138
AC XY:
1
AN XY:
723528
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.00000831
AC:
1
EpiCase
AF:
0.00
EpiControl
AF:
0.0000595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.47
BayesDel_addAF
Uncertain
0.093
D
BayesDel_noAF
Benign
-0.10
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Pathogenic
0.88
D;.;.;D
Eigen
Uncertain
0.54
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Benign
0.70
D
LIST_S2
Uncertain
0.88
.;D;T;D
M_CAP
Pathogenic
0.53
D
MetaRNN
Uncertain
0.45
T;T;T;T
MetaSVM
Uncertain
0.37
D
MutationAssessor
Uncertain
2.3
M;.;.;M
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-2.2
N;.;.;N
REVEL
Uncertain
0.48
Sift
Uncertain
0.0020
D;.;.;D
Sift4G
Uncertain
0.0030
D;.;.;D
Polyphen
0.99
D;.;.;D
Vest4
0.51
MutPred
0.38
Loss of phosphorylation at S8 (P = 0.0034);Loss of phosphorylation at S8 (P = 0.0034);Loss of phosphorylation at S8 (P = 0.0034);Loss of phosphorylation at S8 (P = 0.0034);
MVP
0.69
MPC
1.1
ClinPred
0.81
D
GERP RS
4.8
Varity_R
0.47

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs779204525; hg19: chr10-17271444; API