10-13108903-TGC-T

Variant names:

• chr10-13108903-TGC-T
• rs145112217
• NM_001008212.2:c.-11-205_-11-204delCG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001008212.2(OPTN):​c.-11-205_-11-204delCG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000172 in 477,526 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00012 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00019 (0 hom.)
• Consequence: OPTN NM_001008212.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 0 publications found

Genes affected

OPTN (HGNC:17142): (optineurin) This gene encodes the coiled-coil containing protein optineurin. Optineurin may play a role in normal-tension glaucoma and adult-onset primary open angle glaucoma. Optineurin interacts with adenovirus E3-14.7K protein and may utilize tumor necrosis factor-alpha or Fas-ligand pathways to mediate apoptosis, inflammation or vasoconstriction. Optineurin may also function in cellular morphogenesis and membrane trafficking, vesicle trafficking, and transcription activation through its interactions with the RAB8, huntingtin, and transcription factor IIIA proteins. Alternative splicing results in multiple transcript variants encoding the same protein. [provided by RefSeq, Jul 2008]

OPTN Gene-Disease associations (from GenCC):

• amyotrophic lateral sclerosis type 12

  Inheritance: AD, SD, AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine, ClinGen, Genomics England PanelApp
• glaucoma, normal tension, susceptibility to

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• glaucoma 1, open angle, E

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• amyotrophic lateral sclerosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001008212.2. 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
	OPTN	NM_001008212.2	MANE Select	c.-11-205_-11-204delCG		intron	N/A	NP_001008213.1	Q96CV9-1
	OPTN	NM_001008211.1		c.-80-55_-80-54delCG		intron	N/A	NP_001008212.1	Q96CV9-1
	OPTN	NM_001008213.1		c.-65-55_-65-54delCG		intron	N/A	NP_001008214.1	Q96CV9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPTN	ENST00000378747.8	TSL:1 MANE Select	c.-11-205_-11-204delCG		intron	N/A	ENSP00000368021.3	Q96CV9-1
	OPTN	ENST00000378748.7	TSL:1	c.-80-55_-80-54delCG		intron	N/A	ENSP00000368022.3	Q96CV9-1
	OPTN	ENST00000378757.6	TSL:1	c.-11-205_-11-204delCG		intron	N/A	ENSP00000368032.2	Q96CV9-1

Frequencies

GnomAD3 genomes AF: 0.000120 AC: 16 AN: 133664 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000247

Gnomad FIN AF: 0.000619

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000134

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000192 AC: 66 AN: 343776 Hom.: 0 AF XY: 0.000245 AC XY: 45 AN XY: 183610

African (AFR) AF: 0.0000917 AC: 1 AN: 10906

American (AMR) AF: 0.000305 AC: 6 AN: 19688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10680

East Asian (EAS) AF: 0.0000929 AC: 2 AN: 21526

South Asian (SAS) AF: 0.000554 AC: 23 AN: 41536

European-Finnish (FIN) AF: 0.000685 AC: 14 AN: 20440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1316

European-Non Finnish (NFE) AF: 0.0000907 AC: 18 AN: 198460

Other (OTH) AF: 0.000104 AC: 2 AN: 19224

GnomAD4 genome AF: 0.000120 AC: 16 AN: 133750 Hom.: 0 Cov.: 30 AF XY: 0.000123 AC XY: 8 AN XY: 65266

African (AFR) AF: 0.0000267 AC: 1 AN: 37394

American (AMR) AF: 0.00 AC: 0 AN: 12600

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3006

East Asian (EAS) AF: 0.00 AC: 0 AN: 4298

South Asian (SAS) AF: 0.000248 AC: 1 AN: 4038

European-Finnish (FIN) AF: 0.000619 AC: 6 AN: 9698

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 246

European-Non Finnish (NFE) AF: 0.000134 AC: 8 AN: 59792

Other (OTH) AF: 0.00 AC: 0 AN: 1778

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-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: rs145112217; hg19: chr10-13150903;