7-128772566-A-G

Variant names:

• chr7-128772566-A-G
• NM_001385125.1:c.1012T>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001385125.1(OPN1SW):​c.1012T>C​(p.Ser338Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. S338S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: OPN1SW NM_001385125.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.12

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPN1SW	NM_001385125.1	c.1012T>C	p.Ser338Pro	missense_variant	Exon 5 of 5	ENST00000249389.3	NP_001372054.1
CALU	NM_001219.5	c.*3399A>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000249364.9	NP_001210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPN1SW	ENST00000249389.3	c.1012T>C	p.Ser338Pro	missense_variant	Exon 5 of 5	1	NM_001385125.1	ENSP00000249389.3
CALU	ENST00000249364.9	c.*3399A>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_001219.5	ENSP00000249364.4
CALU	ENST00000542996.7	c.*3399A>G		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000438248.1
CALU	ENST00000449187.7	c.*3399A>G		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000408838.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461872 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 02, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1021T>C (p.S341P) alteration is located in exon 5 (coding exon 5) of the OPN1SW gene. This alteration results from a T to C substitution at nucleotide position 1021, causing the serine (S) at amino acid position 341 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.060	T
BayesDel_noAF	Benign	-0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.56	D
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	0.050	D
MutationAssessor	Pathogenic	3.2	M
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.6	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	D
Vest4		0.54
MutPred		0.27		Loss of phosphorylation at S341 (P = 0.0268);
MVP		0.89
MPC		0.75
ClinPred		0.96	D
GERP RS		4.4
Varity_R		0.38
gMVP		0.33

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-128412620;