7-128772592-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4BS2

The NM_001385125.1(OPN1SW):c.986C>A(p.Ser329Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,614,086 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 1 hom. )

Consequence

OPN1SW
NM_001385125.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.72

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]

OPN1SW links:

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]

CALU links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.36665887).

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPN1SW	NM_001385125.1 link	c.986C>A	p.Ser329Tyr	missense_variant	Exon 5 of 5	ENST00000249389.3	NP_001372054.1
CALU	NM_001219.5 link	c.*3425G>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000249364.9	NP_001210.1	O43852-1Q6IAW5B3KQF5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
OPN1SW	ENST00000249389.3 link	c.986C>A	p.Ser329Tyr	missense_variant	Exon 5 of 5	1	NM_001385125.1	ENSP00000249389.3	P03999
CALU	ENST00000249364.9 link	c.*3425G>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_001219.5	ENSP00000249364.4	O43852-1
CALU	ENST00000542996.7 link	c.*3425G>T		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000438248.1	O43852-4
CALU	ENST00000449187.7 link	c.*3425G>T		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000408838.2	O43852-2

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

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

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251464

AF XY:

0.0000589

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461876

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

33480

Gnomad4 AMR exome

AF:

0.000224

AC:

AN:

44724

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

26136

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39698

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

86258

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

53420

Gnomad4 NFE exome

AF:

0.00

AC:

AN:

1111996

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

60396

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000788

AC:

AN:

152210

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.000785

AC:

0.000785032

AN:

0.000785032

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00

AC:

AN:

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000642

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Feb 01, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. 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 C15"). This variant has not been reported in the literature in individuals affected with OPN1SW-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.03%). This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 332 of the OPN1SW protein (p.Ser332Tyr). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.26

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.58

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.022

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.56

MutationAssessor

Pathogenic

3.0

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.026

Polyphen

0.98

Vest4

0.48

MutPred

0.17

Loss of methylation at K334 (P = 0.0543);

MVP

0.68

MPC

0.68

ClinPred

0.52

GERP RS

5.7

Varity_R

0.21

gMVP

0.35

Mutation Taster

=85/15

polymorphism

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over