1-203496114-G-C

Position:

• chr1-203496114-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014359.4(OPTC):​c.109G>C​(p.Glu37Gln) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: OPTC NM_014359.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11

Genes affected

OPTC (HGNC:8158): (opticin) Opticin belongs to class III of the small leucine-rich repeat protein (SLRP) family. Members of this family are typically associated with the extracellular matrix. Opticin is present in significant quantities in the vitreous of the eye and also localizes to the cornea, iris, ciliary body, optic nerve, choroid, retina, and fetal liver. Opticin may noncovalently bind collagen fibrils and regulate fibril morphology, spacing, and organization. The opticin gene is mapped to a region of chromosome 1 that is associated with the inherited eye diseases age-related macular degeneration (AMD) and posterior column ataxia with retinosa pigmentosa (AXPC1). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1626148).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPTC	NM_014359.4	c.109G>C	p.Glu37Gln	missense_variant	2/8	ENST00000367222.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPTC	ENST00000367222.7	c.109G>C	p.Glu37Gln	missense_variant	2/8	1	NM_014359.4	P1
OPTC	ENST00000448911.1	c.109G>C	p.Glu37Gln	missense_variant	1/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

The c.109G>C (p.E37Q) alteration is located in exon 2 (coding exon 1) of the OPTC gene. This alteration results from a G to C substitution at nucleotide position 109, causing the glutamic acid (E) at amino acid position 37 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T;T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.44	T;T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.18
Sift	Benign	0.042	D;T
Sift4G	Benign	0.064	T;T
Polyphen		0.97	D;.
Vest4		0.16
MutPred		0.15		Loss of phosphorylation at S40 (P = 0.0953);Loss of phosphorylation at S40 (P = 0.0953);
MVP		0.72
MPC		0.36
ClinPred		0.35	T
GERP RS		1.9
Varity_R		0.056
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-203465242;