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GeneBe

7-128772618-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001385125.1(OPN1SW):c.960G>A(p.Met320Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

OPN1SW
NM_001385125.1 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.807
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.09438658).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OPN1SWNM_001385125.1 linkuse as main transcriptc.960G>A p.Met320Ile missense_variant 5/5 ENST00000249389.3
CALUNM_001219.5 linkuse as main transcriptc.*3451C>T 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.960G>A p.Met320Ile missense_variant 5/51 NM_001385125.1 P1
CALUENST00000249364.9 linkuse as main transcriptc.*3451C>T 3_prime_UTR_variant 7/71 NM_001219.5 O43852-1
CALUENST00000449187.7 linkuse as main transcriptc.*3451C>T 3_prime_UTR_variant 7/71 P1O43852-2
CALUENST00000542996.7 linkuse as main transcriptc.*3451C>T 3_prime_UTR_variant 8/81 O43852-4

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000199
AC:
5
AN:
251442
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135892
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461868
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000659
Hom.:
0
ExAC
AF:
0.0000165
AC:
2

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 testingInvitaeJun 22, 2022Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In 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. This variant has not been reported in the literature in individuals affected with OPN1SW-related conditions. This variant is present in population databases (rs755147227, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 323 of the OPN1SW protein (p.Met323Ile). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.46
CADD
Benign
16
DANN
Benign
0.74
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.31
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.0065
T
MetaRNN
Benign
0.094
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L
MutationTaster
Benign
0.98
D
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-0.65
N
REVEL
Benign
0.033
Sift
Benign
0.54
T
Sift4G
Benign
0.42
T
Polyphen
0.0
B
Vest4
0.34
MutPred
0.22
Loss of disorder (P = 0.0567);
MVP
0.34
MPC
0.17
ClinPred
0.064
T
GERP RS
3.7
Varity_R
0.083
gMVP
0.21

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs755147227; hg19: chr7-128412672; API