10-17229477-G-A

Position:

• chr10-17229477-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Moderate BS2

The NM_003380.5(VIM):​c.55G>A​(p.Gly19Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000344 in 1,454,392 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: VIM NM_003380.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.24

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_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24028248).
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VIM	NM_003380.5	c.55G>A	p.Gly19Ser	missense_variant	2/10	ENST00000544301.7	NP_003371.2
VIM-AS1	NR_108061.1	n.509C>T		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VIM	ENST00000544301.7	c.55G>A	p.Gly19Ser	missense_variant	2/10	1	NM_003380.5	ENSP00000446007	P1
VIM-AS1	ENST00000605833.2	n.542C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000344 AC: 5 AN: 1454392 Hom.: 0 Cov.: 33 AF XY: 0.00000415 AC XY: 3 AN XY: 723658

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: 0.0000582

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000836 AC: 1

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 27, 2023

The c.55G>A (p.G19S) alteration is located in exon 2 (coding exon 1) of the VIM gene. This alteration results from a G to A substitution at nucleotide position 55, causing the glycine (G) at amino acid position 19 to be replaced by a serine (S). 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	Benign	0.080
BayesDel_addAF	Benign	0.010	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.49	T;.;.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.81	.;T;T;T
M_CAP	Pathogenic	0.61	D
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.42	T
MutationAssessor	Benign	0.58	N;.;.;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.68	N;.;.;N
REVEL	Benign	0.22
Sift	Benign	0.43	T;.;.;T
Sift4G	Benign	0.74	T;.;.;T
Polyphen		0.0010	B;.;.;B
Vest4		0.13
MutPred		0.36		Gain of phosphorylation at G19 (P = 0.0035);Gain of phosphorylation at G19 (P = 0.0035);Gain of phosphorylation at G19 (P = 0.0035);Gain of phosphorylation at G19 (P = 0.0035);
MVP		0.75
MPC		0.69
ClinPred		0.079	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs771023210; hg19: chr10-17271476;