rs104894031

Variant names:

• chr7-128775556-C-G
• rs104894031
• NM_001385125.1:c.226G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-128775556-C-G
• chr7-128775556-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001385125.1(OPN1SW):​c.226G>C​(p.Gly76Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Synonymous variant affecting the same amino acid position (i.e. G76G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: OPN1SW NM_001385125.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617
• 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]

OPN1SW Gene-Disease associations (from GenCC):

• blue color blindness

  Inheritance: AD Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.98

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
OPN1SW	NM_001385125.1	c.226G>C	p.Gly76Arg	missense_variant	Exon 1 of 5	ENST00000249389.3	NP_001372054.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
OPN1SW	ENST00000249389.3	c.226G>C	p.Gly76Arg	missense_variant	Exon 1 of 5	1	NM_001385125.1	ENSP00000249389.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.14
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.35	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.55	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.043	D
MetaRNN	Pathogenic	0.98	D
MetaSVM	Uncertain	-0.044	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.62
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.94	P
Vest4		0.81
MutPred		0.95		Gain of methylation at G79 (P = 0.0062);
MVP		0.91
MPC		0.25
ClinPred		0.82	D
GERP RS		4.4
PromoterAI		0.011	Neutral
Varity_R		0.75
gMVP		0.84
Mutation Taster		=35/65	disease causing

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: rs104894031; hg19: chr7-128415610;