7-128772632-A-T

Variant names:

• chr7-128772632-A-T
• rs946529537
• NM_001385125.1:c.946T>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001385125.1(OPN1SW):​c.946T>A​(p.Cys316Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C316G) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: OPN1SW NM_001385125.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.50
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.757

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385125.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN1SW	NM_001385125.1	MANE Select	c.946T>A	p.Cys316Ser	missense	Exon 5 of 5	NP_001372054.1	P03999
	CALU	NM_001219.5	MANE Select	c.*3465A>T		3_prime_UTR	Exon 7 of 7	NP_001210.1	Q6IAW5
	CALU	NM_001199671.2		c.*3465A>T		3_prime_UTR	Exon 8 of 8	NP_001186600.1	O43852-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN1SW	ENST00000249389.3	TSL:1 MANE Select	c.946T>A	p.Cys316Ser	missense	Exon 5 of 5	ENSP00000249389.3	P03999
	CALU	ENST00000249364.9	TSL:1 MANE Select	c.*3465A>T		3_prime_UTR	Exon 7 of 7	ENSP00000249364.4	O43852-1
	CALU	ENST00000542996.7	TSL:1	c.*3465A>T		3_prime_UTR	Exon 8 of 8	ENSP00000438248.1	O43852-4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152186 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74346

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.32
BayesDel_addAF	Benign	0.0040	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.56	D
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.026	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		6.5
PrimateAI	Uncertain	0.52	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Benign	0.25
Sift	Uncertain	0.026	D
Sift4G	Benign	0.099	T
Polyphen		0.93	P
Vest4		0.65
MutPred		0.51		Loss of catalytic residue at M317 (P = 5e-04)
MVP		0.63
MPC		0.46
ClinPred		0.98	D
GERP RS		4.3
Varity_R		0.26
gMVP		0.21
Mutation Taster		=77/23	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

Other links and lift over

dbSNP: rs946529537; hg19: chr7-128412686;