rs11545551

Variant names:

• chr10-17229976-T-C
• rs11545551
• NM_003380.5:c.554T>C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_003380.5(VIM):​c.554T>C​(p.Leu185Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VIM NM_003380.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.11

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.949

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VIM	NM_003380.5	c.554T>C	p.Leu185Pro	missense_variant	Exon 2 of 10	ENST00000544301.7	NP_003371.2
VIM-AS1	NR_108061.1	n.10A>G		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VIM	ENST00000544301.7	c.554T>C	p.Leu185Pro	missense_variant	Exon 2 of 10	1	NM_003380.5	ENSP00000446007.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	1.0
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.46
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.97	D;D
Eigen	Pathogenic	0.85
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Pathogenic	0.46	D
MetaRNN	Pathogenic	0.95	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	4.2	H;H
PrimateAI	Uncertain	0.77	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Pathogenic	0.90
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.96
MutPred		0.75		Loss of stability (P = 0.0051);Loss of stability (P = 0.0051);
MVP		0.96
MPC		1.6
ClinPred		1.0	D
GERP RS		5.2
Varity_R		0.99

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11545551; hg19: chr10-17271975;