rs758942502

Variant names:

• chr10-13109168-C-A
• rs758942502
• NM_001008212.2:c.46C>A

Your query was ambiguous. Multiple possible variants found:

• chr10-13109168-C-A
• chr10-13109168-C-G
• chr10-13109168-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001008212.2(OPTN):​c.46C>A​(p.Pro16Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P16A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: OPTN NM_001008212.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127
• Publications: 4 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):

• glaucoma, normal tension, susceptibility to

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• amyotrophic lateral sclerosis type 12

  Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics, Genomics England PanelApp
• glaucoma 1, open angle, E

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

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07832357).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPTN	NM_001008212.2	c.46C>A	p.Pro16Thr	missense_variant	Exon 3 of 15	ENST00000378747.8	NP_001008213.1
OPTN	NM_001008211.1	c.46C>A	p.Pro16Thr	missense_variant	Exon 4 of 16		NP_001008212.1
OPTN	NM_001008213.1	c.46C>A	p.Pro16Thr	missense_variant	Exon 4 of 16		NP_001008214.1
OPTN	NM_021980.4	c.46C>A	p.Pro16Thr	missense_variant	Exon 2 of 14		NP_068815.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPTN	ENST00000378747.8	c.46C>A	p.Pro16Thr	missense_variant	Exon 3 of 15	1	NM_001008212.2	ENSP00000368021.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	14
DANN	Benign	0.61
DEOGEN2	Benign	0.14	T;.;T;.;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.24	N
LIST_S2	Uncertain	0.86	.;.;.;D;.;D
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.078	T;T;T;T;T;T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	1.7	L;L;L;L;L;L
PhyloP100		0.13
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.89	N;N;N;N;N;N
REVEL	Benign	0.21
Sift	Benign	0.071	T;T;T;T;T;T
Sift4G	Benign	0.74	T;T;T;T;T;T
Polyphen		0.062	B;B;B;B;B;B
Vest4		0.19
MutPred		0.093		Gain of phosphorylation at P16 (P = 0.0183);Gain of phosphorylation at P16 (P = 0.0183);Gain of phosphorylation at P16 (P = 0.0183);Gain of phosphorylation at P16 (P = 0.0183);Gain of phosphorylation at P16 (P = 0.0183);Gain of phosphorylation at P16 (P = 0.0183);
MVP		0.91
MPC		0.44
ClinPred		0.12	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.040
gMVP		0.51
Mutation Taster		=45/55	disease causing

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: rs758942502; hg19: chr10-13151168;