Genetic Variant NM_003380.5:c.82C>G (chr10-17229504-C-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003380.5(VIM):c.82C>G(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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

VIM
NM_003380.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.235

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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17952159).

BS2

High AC in GnomAdExome4 at 12 AD gene.

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.82C>G	p.Arg28Gly	missense	Exon 2 of 10	NP_003371.2	P08670
	VIM-AS1	NR_108061.1		n.482G>C		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.82C>G	p.Arg28Gly	missense	Exon 2 of 10	ENSP00000446007.1	P08670
VIM	ENST00000224237.9	TSL:1	c.82C>G	p.Arg28Gly	missense	Exon 1 of 9	ENSP00000224237.5	P08670
VIM	ENST00000946784.1		c.82C>G	p.Arg28Gly	missense	Exon 2 of 10	ENSP00000616843.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000824

AC:

AN:

1455760

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

724322

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33392

American (AMR)

AF:

0.00

AC:

AN:

44612

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26050

East Asian (EAS)

AF:

0.00

AC:

AN:

39604

South Asian (SAS)

AF:

0.00

AC:

AN:

85994

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4814

European-Non Finnish (NFE)

AF:

0.00000720

AC:

AN:

1111162

Other (OTH)

AF:

0.0000666

AC:

AN:

60084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Cataract 30 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

0.0057

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Uncertain

0.59

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.76

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.75

M_CAP

Pathogenic

0.67

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.73

MutationAssessor

Benign

0.63

PhyloP100

0.23

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.4

REVEL

Benign

0.28

Sift

Benign

0.12

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.32

MutPred

0.37

Loss of methylation at R28 (P = 0.0276)

MVP

0.29

MPC

0.66

ClinPred

0.075

GERP RS

4.5

PromoterAI

-0.065

Neutral

(source)

Varity_R

0.15

Mutation Taster

=91/9

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over