Genetic Variant NM_003380.5:c.281C>T (chr10-17229703-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003380.5(VIM):c.281C>T(p.Thr94Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,419,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T94T) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

VIM
NM_003380.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

Publications

0 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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.281C>T	p.Thr94Ile	missense	Exon 2 of 10	NP_003371.2	P08670
	VIM-AS1	NR_108061.1		n.283G>A		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.281C>T	p.Thr94Ile	missense	Exon 2 of 10	ENSP00000446007.1	P08670
VIM	ENST00000224237.9	TSL:1	c.281C>T	p.Thr94Ile	missense	Exon 1 of 9	ENSP00000224237.5	P08670
VIM	ENST00000946784.1		c.281C>T	p.Thr94Ile	missense	Exon 2 of 10	ENSP00000616843.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.05e-7

AC:

AN:

1419178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32514

American (AMR)

AF:

0.00

AC:

AN:

38000

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25348

East Asian (EAS)

AF:

0.00

AC:

AN:

37268

South Asian (SAS)

AF:

0.0000123

AC:

AN:

81284

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50378

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089806

Other (OTH)

AF:

0.00

AC:

AN:

58856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.83

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.12

MetaRNN

Uncertain

0.50

MetaSVM

Uncertain

0.087

MutationAssessor

Uncertain

2.3

PhyloP100

3.1

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.48

Sift

Benign

0.077

Sift4G

Benign

0.17

Polyphen

0.41

Vest4

0.54

MutPred

0.47

Loss of disorder (P = 0.0427)

MVP

0.38

MPC

0.73

ClinPred

0.95

GERP RS

4.4

PromoterAI

0.018

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.21

Mutation Taster

=74/26

polymorphism

(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