rs1801631857

Variant names:

• chr7-128772619-A-C
• rs1801631857
• NM_001385125.1:c.959T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-128772619-A-C
• chr7-128772619-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001385125.1(OPN1SW):​c.959T>G​(p.Met320Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M320I) has been classified as Uncertain significance.

• 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: 5.50
• 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 2 ACMG points.

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

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.959T>G	p.Met320Arg	missense	Exon 5 of 5	NP_001372054.1	P03999
	CALU	NM_001219.5	MANE Select	c.*3452A>C		3_prime_UTR	Exon 7 of 7	NP_001210.1	Q6IAW5
	CALU	NM_001199671.2		c.*3452A>C		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.959T>G	p.Met320Arg	missense	Exon 5 of 5	ENSP00000249389.3	P03999
	CALU	ENST00000249364.9	TSL:1 MANE Select	c.*3452A>C		3_prime_UTR	Exon 7 of 7	ENSP00000249364.4	O43852-1
	CALU	ENST00000542996.7	TSL:1	c.*3452A>C		3_prime_UTR	Exon 8 of 8	ENSP00000438248.1	O43852-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.32
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.013	T
MetaRNN	Uncertain	0.66	D
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.5
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.11
Sift	Benign	0.35	T
Sift4G	Benign	0.42	T
Polyphen		0.71	P
Vest4		0.83
MutPred		0.28		Gain of phosphorylation at T324 (P = 0.0985)
MVP		0.58
MPC		0.24
ClinPred		0.60	D
GERP RS		5.5
Varity_R		0.19
gMVP		0.41
Mutation Taster		=71/29	polymorphism

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

Other links and lift over

dbSNP: rs1801631857; hg19: chr7-128412673;