10-17229873-G-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 4P and 1B. PM2PM5BP4

The NM_003380.5(VIM):c.451G>C(p.Glu151Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,250 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. E151K) has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

VIM
NM_003380.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.04

Publications

12 publications found

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 links:

VIM-AS1 (HGNC:44879): (VIM antisense RNA 1)

VIM-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM5

Other missense variant is known to change same aminoacid residue: Variant chr10-17229873-G-A is described in ClinVar as Pathogenic. ClinVar VariationId is 12199.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.34932822).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003380.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIM	NM_003380.5	MANE Select	c.451G>C	p.Glu151Gln	missense	Exon 2 of 10	NP_003371.2	P08670
	VIM-AS1	NR_108061.1		n.113C>G		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VIM	ENST00000544301.7	TSL:1 MANE Select	c.451G>C	p.Glu151Gln	missense	Exon 2 of 10	ENSP00000446007.1	P08670
VIM	ENST00000224237.9	TSL:1	c.451G>C	p.Glu151Gln	missense	Exon 1 of 9	ENSP00000224237.5	P08670
VIM	ENST00000946784.1		c.451G>C	p.Glu151Gln	missense	Exon 2 of 10	ENSP00000616843.1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41470

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Pathogenic

0.19

BayesDel_noAF

Uncertain

0.030

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Uncertain

0.52

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.92

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.35

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

0.93

PhyloP100

8.0

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.030

REVEL

Uncertain

0.54

Sift

Benign

0.63

Sift4G

Benign

0.43

Polyphen

0.032

Vest4

0.47

MutPred

0.61

Gain of MoRF binding (P = 0.0423)

MVP

0.77

MPC

0.54

ClinPred

0.83

GERP RS

3.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

Mutation Taster

=39/61

disease causing

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over