Menu
GeneBe

7-128772632-A-C

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM5PP3BS2

The NM_001385125.1(OPN1SW):c.946T>G(p.Cys316Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C316R) has been classified as Likely pathogenic.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

OPN1SW
NM_001385125.1 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.50
Variant links:
Genes affected
OPN1SW (HGNC:1012): (opsin 1, short wave sensitive) This gene belongs to the G-protein coupled receptor 1 family, opsin subfamily. It encodes the blue cone pigment gene which is one of three types of cone photoreceptors responsible for normal color vision. Defects in this gene are the cause of tritan color blindness (tritanopia). Affected individuals lack blue and yellow sensory mechanisms while retaining those for red and green. Defective blue vision is characteristic. [provided by RefSeq, Jul 2008]
CALU (HGNC:1458): (calumenin) The product of this gene is a calcium-binding protein localized in the endoplasmic reticulum (ER) and it is involved in such ER functions as protein folding and sorting. This protein belongs to a family of multiple EF-hand proteins (CERC) that include reticulocalbin, ERC-55, and Cab45 and the product of this gene. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Oct 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

PM5
Other missense variant is known to change same aminoacid residue: Variant chr7-128772632-A-G is described in Lovd as [Likely_pathogenic].
PP3
MetaRNN computational evidence supports a deleterious effect, 0.776
BS2
High AC in GnomAdExome4 at 23 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OPN1SWNM_001385125.1 linkuse as main transcriptc.946T>G p.Cys316Gly missense_variant 5/5 ENST00000249389.3
CALUNM_001219.5 linkuse as main transcriptc.*3465A>C 3_prime_UTR_variant 7/7 ENST00000249364.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
OPN1SWENST00000249389.3 linkuse as main transcriptc.946T>G p.Cys316Gly missense_variant 5/51 NM_001385125.1 P1
CALUENST00000249364.9 linkuse as main transcriptc.*3465A>C 3_prime_UTR_variant 7/71 NM_001219.5 O43852-1
CALUENST00000449187.7 linkuse as main transcriptc.*3465A>C 3_prime_UTR_variant 7/71 P1O43852-2
CALUENST00000542996.7 linkuse as main transcriptc.*3465A>C 3_prime_UTR_variant 8/81 O43852-4

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461860
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingInvitaeMay 19, 2021In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with OPN1SW-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with glycine at codon 319 of the OPN1SW protein (p.Cys319Gly). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and glycine. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.020
T
BayesDel_noAF
Benign
-0.27
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Uncertain
0.56
D
Eigen
Pathogenic
0.69
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.036
D
MetaRNN
Pathogenic
0.78
D
MetaSVM
Benign
-0.74
T
MutationAssessor
Uncertain
2.3
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.49
T
PROVEAN
Uncertain
-4.0
D
REVEL
Benign
0.25
Sift
Benign
0.26
T
Sift4G
Benign
0.23
T
Polyphen
0.98
D
Vest4
0.66
MutPred
0.52
Loss of catalytic residue at M317 (P = 8e-04);
MVP
0.67
MPC
0.42
ClinPred
0.93
D
GERP RS
4.3
Varity_R
0.21
gMVP
0.18

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs946529537; hg19: chr7-128412686; API