10-17229651-G-T

Variant names:

• chr10-17229651-G-T
• rs184701100
• NM_003380.5:c.229G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003380.5(VIM):​c.229G>T​(p.Val77Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V77M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: VIM NM_003380.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06772348).

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.229G>T	p.Val77Leu	missense	Exon 2 of 10	NP_003371.2	P08670
	VIM-AS1	NR_108061.1		n.335C>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIM	ENST00000544301.7	TSL:1 MANE Select	c.229G>T	p.Val77Leu	missense	Exon 2 of 10	ENSP00000446007.1	P08670
	VIM	ENST00000224237.9	TSL:1	c.229G>T	p.Val77Leu	missense	Exon 1 of 9	ENSP00000224237.5	P08670
	VIM	ENST00000946784.1		c.229G>T	p.Val77Leu	missense	Exon 2 of 10	ENSP00000616843.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	15
DANN	Benign	0.92
DEOGEN2	Benign	0.41	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.20	N
LIST_S2	Benign	0.70	T
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.068	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.68
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.18
Sift	Benign	0.94	T
Sift4G	Benign	0.38	T
Polyphen		0.0010	B
Vest4		0.039
MutPred		0.52		Loss of MoRF binding (P = 0.0954)
MVP		0.37
MPC		0.44
ClinPred		0.050	T
GERP RS		1.1
PromoterAI		0.00040	Neutral
Varity_R		0.22
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs184701100; hg19: chr10-17271650; COSMIC: COSV56407124; COSMIC: COSV56407124;