chr10-86660041-C-T
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_033282.4(OPN4):c.947C>T(p.Ala316Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
OPN4
NM_033282.4 missense
NM_033282.4 missense
Scores
1
6
10
Clinical Significance
Conservation
PhyloP100: 3.35
Genes affected
OPN4 (HGNC:14449): (opsin 4) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. This gene encodes a photoreceptive opsin protein that is expressed within the ganglion and amacrine cell layers of the retina. In mouse, retinal ganglion cell axons expressing this gene projected to the suprachiasmatic nucleus and other brain nuclei involved in circadian photoentrainment. In mouse, this protein is coupled to a transient receptor potential (TRP) ion channel through a G protein signaling pathway and produces a physiologic light response via membrane depolarization and increased intracellular calcium. The protein functions as a sensory photopigment and may also have photoisomerase activity. Experiments with knockout mice indicate that this gene attenuates, but does not abolish, photoentrainment. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OPN4 | NM_033282.4 | c.947C>T | p.Ala316Val | missense_variant | 6/10 | ENST00000241891.10 | |
LOC105378409 | XR_001747526.2 | n.382-1747G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OPN4 | ENST00000241891.10 | c.947C>T | p.Ala316Val | missense_variant | 6/10 | 1 | NM_033282.4 | P1 | |
OPN4 | ENST00000372071.7 | c.980C>T | p.Ala327Val | missense_variant | 7/11 | 1 | |||
OPN4 | ENST00000686083.1 | n.1646C>T | non_coding_transcript_exon_variant | 3/3 | |||||
OPN4 | ENST00000690949.1 | n.981C>T | non_coding_transcript_exon_variant | 7/11 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727244
GnomAD4 exome
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6
AN:
1461862
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32
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2
AN XY:
727244
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GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 03, 2024 | The c.980C>T (p.A327V) alteration is located in exon 7 (coding exon 7) of the OPN4 gene. This alteration results from a C to T substitution at nucleotide position 980, causing the alanine (A) at amino acid position 327 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N
REVEL
Benign
Sift
Benign
T;D;T
Sift4G
Benign
T;T;T
Polyphen
D;P;P
Vest4
MutPred
Loss of sheet (P = 0.1158);.;Loss of sheet (P = 0.1158);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at