10-17229445-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.866

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)

ACMG classification

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	UniProt
VIM	NM_003380.5	c.23C>T	p.Ser8Leu	missense_variant	2/10	ENST00000544301.7
VIM-AS1	NR_108061.1	n.541G>A		non_coding_transcript_exon_variant	1/3

Ensembl

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

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1454142 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 2 AN XY: 723528

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.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.68	D;.;.;D
Eigen	Benign	0.18
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Benign	0.65	D
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	1.9	L;.;.;L
MutationTaster	Benign	0.90	D;D
PrimateAI	Pathogenic	0.80	T
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	D
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

Other links and lift over

dbSNP: rs779204525; hg19: chr10-17271444; COSMIC: COSV99813389; COSMIC: COSV99813389;