Variant chr10-17229445-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003380.5(VIM):c.23C>T(p.Ser8Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,454,142 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

VIM
NM_003380.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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 links:

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

VIM-AS1 links:

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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/exons	MANE	Protein	UniProt
VIM	NM_003380.5 linkuse as main transcript	c.23C>T	p.Ser8Leu	missense_variant	2/10	ENST00000544301.7	NP_003371.2
VIM-AS1	NR_108061.1 linkuse as main transcript	n.541G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIM	ENST00000544301.7 linkuse as main transcript	c.23C>T	p.Ser8Leu	missense_variant	2/10	1	NM_003380.5	ENSP00000446007	P1
VIM-AS1	ENST00000605833.2 linkuse as main transcript	n.574G>A		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1454142

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Uncertain

0.052

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

D;.;.;D

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.88

.;D;T;D

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.33

T;T;T;T

MetaSVM

Uncertain

-0.18

MutationAssessor

Benign

1.9

L;.;.;L

MutationTaster

Benign

0.90

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.6

N;.;.;N

REVEL

Uncertain

0.33

Sift

Uncertain

0.019

D;.;.;D

Sift4G

Benign

0.062

T;.;.;T

Polyphen

0.75

P;.;.;P

Vest4

0.41

MutPred

0.37

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

0.44

MPC

0.74

ClinPred

0.80

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.23

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.23

Position offset: 16

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over