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GeneBe

7-128772544-T-C

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001385125.1(OPN1SW):c.1034A>G(p.Asn345Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

OPN1SW
NM_001385125.1 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.900
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 Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.042689383).
BS2
High AC in GnomAdExome4 at 35 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OPN1SWNM_001385125.1 linkuse as main transcriptc.1034A>G p.Asn345Ser missense_variant 5/5 ENST00000249389.3
CALUNM_001219.5 linkuse as main transcriptc.*3377T>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.1034A>G p.Asn345Ser missense_variant 5/51 NM_001385125.1 P1
CALUENST00000249364.9 linkuse as main transcriptc.*3377T>C 3_prime_UTR_variant 7/71 NM_001219.5 O43852-1
CALUENST00000449187.7 linkuse as main transcriptc.*3377T>C 3_prime_UTR_variant 7/71 P1O43852-2
CALUENST00000542996.7 linkuse as main transcriptc.*3377T>C 3_prime_UTR_variant 8/81 O43852-4

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152178
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
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
GnomAD3 exomes
AF:
0.0000239
AC:
6
AN:
251468
Hom.:
0
AF XY:
0.0000294
AC XY:
4
AN XY:
135914
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000239
AC:
35
AN:
1461868
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
14
AN XY:
727228
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000671
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:
0.0000261
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152178
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000655
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
Bravo
AF:
0.0000189
ExAC
AF:
0.0000330
AC:
4
EpiCase
AF:
0.000109
EpiControl
AF:
0.0000593

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 testingInvitaeMar 10, 2022In 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with OPN1SW-related conditions. This variant is present in population databases (rs776133013, gnomAD 0.006%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 348 of the OPN1SW protein (p.Asn348Ser). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.060
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
12
DANN
Benign
0.61
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.79
Eigen_PC
Benign
-0.70
FATHMM_MKL
Benign
0.42
N
LIST_S2
Uncertain
0.86
D
M_CAP
Benign
0.0057
T
MetaRNN
Benign
0.043
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
0.98
N
REVEL
Benign
0.10
Sift
Benign
0.84
T
Sift4G
Benign
1.0
T
Polyphen
0.0
B
Vest4
0.13
MutPred
0.15
Gain of phosphorylation at N348 (P = 0.0229);
MVP
0.63
MPC
0.12
ClinPred
0.034
T
GERP RS
-2.0
Varity_R
0.0092
gMVP
0.22

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

Publications

LitVar

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

Other links and lift over

dbSNP: rs776133013; hg19: chr7-128412598; API