10-17229703-C-T

Position:

• chr10-17229703-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: VIM NM_003380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.13

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• 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	c.281C>T	p.Thr94Ile	missense_variant	2/10	ENST00000544301.7	NP_003371.2
VIM-AS1	NR_108061.1	n.283G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIM	ENST00000544301.7	c.281C>T	p.Thr94Ile	missense_variant	2/10	1	NM_003380.5	ENSP00000446007.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1419178 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 702154

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: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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 specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

The c.281C>T (p.T94I) alteration is located in exon 2 (coding exon 1) of the VIM gene. This alteration results from a C to T substitution at nucleotide position 281, causing the threonine (T) at amino acid position 94 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Uncertain	0.074	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.83	D;.;.;D
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Benign	0.70	D
LIST_S2	Uncertain	0.89	.;D;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Uncertain	0.50	D;D;D;D
MetaSVM	Uncertain	0.087	D
MutationAssessor	Uncertain	2.3	M;.;.;M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.4	N;.;.;N
REVEL	Uncertain	0.48
Sift	Benign	0.077	T;.;.;T
Sift4G	Benign	0.17	T;.;.;T
Polyphen		0.41	B;.;.;B
Vest4		0.54
MutPred		0.47		Loss of disorder (P = 0.0427);Loss of disorder (P = 0.0427);Loss of disorder (P = 0.0427);Loss of disorder (P = 0.0427);
MVP		0.38
MPC		0.73
ClinPred		0.95	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-17271702;