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GeneBe

7-128772574-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001385125.1(OPN1SW):c.1004C>T(p.Ser335Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,614,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

OPN1SW
NM_001385125.1 missense

Scores

7
9
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.14
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 -4 ACMG points.

BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
OPN1SWNM_001385125.1 linkuse as main transcriptc.1004C>T p.Ser335Phe missense_variant 5/5 ENST00000249389.3
CALUNM_001219.5 linkuse as main transcriptc.*3407G>A 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.1004C>T p.Ser335Phe missense_variant 5/51 NM_001385125.1 P1
CALUENST00000249364.9 linkuse as main transcriptc.*3407G>A 3_prime_UTR_variant 7/71 NM_001219.5 O43852-1
CALUENST00000449187.7 linkuse as main transcriptc.*3407G>A 3_prime_UTR_variant 7/71 P1O43852-2
CALUENST00000542996.7 linkuse as main transcriptc.*3407G>A 3_prime_UTR_variant 8/81 O43852-4

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251448
Hom.:
0
AF XY:
0.0000442
AC XY:
6
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.000431
Gnomad AMR exome
AF:
0.0000867
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:
0.00000879
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.00000958
AC:
14
AN:
1461868
Hom.:
0
Cov.:
31
AF XY:
0.00000825
AC XY:
6
AN XY:
727230
show subpopulations
Gnomad4 AFR exome
AF:
0.000209
Gnomad4 AMR exome
AF:
0.0000447
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:
0.00000360
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000526
AC:
8
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000672
AC XY:
5
AN XY:
74360
show subpopulations
Gnomad4 AFR
AF:
0.000193
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000966
Hom.:
0
Bravo
AF:
0.0000680
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000330
AC:
4

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 testingInvitaeAug 31, 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 disruptive. 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. ClinVar contains an entry for this variant (Variation ID: 1036080). This variant has not been reported in the literature in individuals affected with OPN1SW-related conditions. This variant is present in population databases (rs376418066, gnomAD 0.04%). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 338 of the OPN1SW protein (p.Ser338Phe). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.32
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Uncertain
-0.080
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.75
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.97
D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.58
D
MetaSVM
Uncertain
0.41
D
MutationAssessor
Pathogenic
3.4
M
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.9
D
REVEL
Uncertain
0.43
Sift
Pathogenic
0.0
D
Sift4G
Pathogenic
0.0
D
Polyphen
1.0
D
Vest4
0.47
MVP
0.94
MPC
0.67
ClinPred
0.87
D
GERP RS
5.7
Varity_R
0.55
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: rs376418066; hg19: chr7-128412628; API