10-17229521-G-C

Variant names:

• chr10-17229521-G-C
• rs531385322
• NM_003380.5:c.99G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_003380.5(VIM):​c.99G>C​(p.Thr33Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,455,950 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T33T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: VIM NM_003380.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.508
• Publications: 0 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=-0.508 with no splicing effect.

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.99G>C	p.Thr33Thr	synonymous	Exon 2 of 10	NP_003371.2	P08670
	VIM-AS1	NR_108061.1		n.465C>G		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.99G>C	p.Thr33Thr	synonymous	Exon 2 of 10	ENSP00000446007.1	P08670
	VIM	ENST00000224237.9	TSL:1	c.99G>C	p.Thr33Thr	synonymous	Exon 1 of 9	ENSP00000224237.5	P08670
	VIM	ENST00000946784.1		c.99G>C	p.Thr33Thr	synonymous	Exon 2 of 10	ENSP00000616843.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455950 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 724362

African (AFR) AF: 0.00 AC: 0 AN: 33408

American (AMR) AF: 0.00 AC: 0 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26058

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39604

South Asian (SAS) AF: 0.00 AC: 0 AN: 85992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5020

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111168

Other (OTH) AF: 0.00 AC: 0 AN: 60100

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.63
PhyloP100		-0.51
PromoterAI		0.023	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs531385322; hg19: chr10-17271520;