10-17235159-C-T

Variant summary

Our verdict is Benign. Variant got -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 splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00002333
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.974

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 474043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-17235159-C-T is described in Lovd as [Likely_benign]. Variant chr10-17235159-C-T is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome 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 gnomad4_exome. There are 5476 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 1019 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VIM	NM_003380.5	c.1009-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000544301.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VIM	ENST00000544301.7	c.1009-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003380.5	P1
VIM	ENST00000224237.9	c.1009-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1		P1
VIM	ENST00000469543.5	c.463-10C>T		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		2
VIM	ENST00000487938.5	c.1009-10C>T		splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		5

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

GnomAD3 exomes AF: 0.00721 AC: 1813 AN: 251328 Hom.: 8 AF XY: 0.00734 AC XY: 997 AN XY: 135866

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 SAS exome AF: 0.00382

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

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.00550

Gnomad4 ASJ exome AF: 0.0181

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00426

Gnomad4 FIN exome AF: 0.00554

Gnomad4 NFE exome AF: 0.00806

Gnomad4 OTH exome AF: 0.00788

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

Gnomad4 AFR AF: 0.00164

Gnomad4 AMR AF: 0.00686

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00477

Gnomad4 FIN AF: 0.00555

Gnomad4 NFE AF: 0.00964

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00651 Hom.: 4

Bravo AF: 0.00689

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 08, 2020

- -

Cataract 30 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	2.5
Dann	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs79719081; hg19: chr10-17277158; COSMIC: COSV56406059; COSMIC: COSV56406059;