10-17235159-C-T

Variant names:

• chr10-17235159-C-T
• rs79719081
• NM_003380.5:c.1009-10C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003380.5(VIM):​c.1009-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00746 in 1,613,968 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0067 (3 hom., cov: 33)
  • Exomes 𝑓: 0.0075 (59 hom.)
• Consequence: VIM NM_003380.5 intron
• Scores: Splicing: ADA: 0.00002333
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.974
• 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 Gene-Disease associations (from GenCC):

• cataract

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• cataract 30

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• pulverulent cataract

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-17235159-C-T is Benign according to our data. Variant chr10-17235159-C-T is described in ClinVar as Benign. ClinVar VariationId is 474043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population mid. GnomAdExome4 allele frequency = 0.00754 (11024/1461636) while in subpopulation MID AF = 0.0269 (155/5766). AF 95% confidence interval is 0.0234. There are 59 homozygotes in GnomAdExome4. There are 5476 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1019 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIM	NM_003380.5	MANE Select	c.1009-10C>T		intron	N/A	NP_003371.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VIM	ENST00000544301.7	TSL:1 MANE Select	c.1009-10C>T		intron	N/A	ENSP00000446007.1
	VIM	ENST00000224237.9	TSL:1	c.1009-10C>T		intron	N/A	ENSP00000224237.5
	VIM	ENST00000469543.5	TSL:2	n.463-10C>T		intron	N/A	ENSP00000431702.1

Frequencies

GnomAD3 genomes AF: 0.00669 AC: 1019 AN: 152214 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00164

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00687

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00476

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00964

Gnomad OTH AF: 0.00860

GnomAD2 exomes AF: 0.00721 AC: 1813 AN: 251328 AF XY: 0.00734

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00558

Gnomad ASJ exome AF: 0.0195

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00476

Gnomad NFE exome AF: 0.00965

Gnomad OTH exome AF: 0.0122

GnomAD4 exome AF: 0.00754 AC: 11024 AN: 1461636 Hom.: 59 Cov.: 31 AF XY: 0.00753 AC XY: 5476 AN XY: 727140

African (AFR) AF: 0.00152 AC: 51 AN: 33476

American (AMR) AF: 0.00550 AC: 246 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0181 AC: 474 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00426 AC: 367 AN: 86246

European-Finnish (FIN) AF: 0.00554 AC: 296 AN: 53404

Middle Eastern (MID) AF: 0.0269 AC: 155 AN: 5766

European-Non Finnish (NFE) AF: 0.00806 AC: 8959 AN: 1111802

Other (OTH) AF: 0.00788 AC: 476 AN: 60390

GnomAD4 genome AF: 0.00669 AC: 1019 AN: 152332 Hom.: 3 Cov.: 33 AF XY: 0.00638 AC XY: 475 AN XY: 74490

African (AFR) AF: 0.00164 AC: 68 AN: 41580

American (AMR) AF: 0.00686 AC: 105 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5192

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4826

European-Finnish (FIN) AF: 0.00555 AC: 59 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.00964 AC: 656 AN: 68024

Other (OTH) AF: 0.00851 AC: 18 AN: 2114

Alfa AF: 0.00810 Hom.: 14

Bravo AF: 0.00689

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cataract 30 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.5
DANN	Benign	0.68
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000023
dbscSNV1_RF	Benign	0.0
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: rs79719081; hg19: chr10-17277158; COSMIC: COSV56406059; COSMIC: COSV56406059;