X-154150890-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_020061.6(OPN1LW):c.347C>A(p.Ser116Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000462 in 1,192,456 control chromosomes in the GnomAD database, including 16 homozygotes. There are 242 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.00032 (1 hom., 5 hem., cov: 18)
  • Exomes 𝑓: 0.00048 (15 hom. 237 hem.)
• Consequence: OPN1LW NM_020061.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.424

Genes affected

OPN1LW (HGNC:9936): (opsin 1, long wave sensitive) This gene encodes for a light absorbing visual pigment of the opsin gene family. The encoded protein is called red cone photopigment or long-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. This gene and the medium-wavelength opsin gene are tandemly arrayed on the X chromosome and frequent unequal recombination and gene conversion may occur between these sequences. X chromosomes may have fusions of the medium- and long-wavelength opsin genes or may have more than one copy of these genes. Defects in this gene are the cause of partial, protanopic colorblindness. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022827089).
• BP6: Variant X-154150890-C-A is Benign according to our data. Variant chrX-154150890-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661786.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154150890-C-A is described in Lovd as [Benign]. Variant chrX-154150890-C-A is described in Lovd as [Likely_benign].
• BS2: High Hemizygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1LW	NM_020061.6	c.347C>A	p.Ser116Tyr	missense_variant	2/6	ENST00000369951.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1LW	ENST00000369951.9	c.347C>A	p.Ser116Tyr	missense_variant	2/6	1	NM_020061.6	P1
OPN1LW	ENST00000463296.1	n.357C>A		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.000320 AC: 34 AN: 106090 Hom.: 1 Cov.: 18 AF XY: 0.000166 AC XY: 5 AN XY: 30046

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000988

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000519

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000344

Gnomad OTH AF: 0.00208

GnomAD3 exomes AF: 0.000505 AC: 91 AN: 180327 Hom.: 4 AF XY: 0.000611 AC XY: 40 AN XY: 65477

Gnomad AFR exome AF: 0.0000772

Gnomad AMR exome AF: 0.00114

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000363

Gnomad SAS exome AF: 0.000317

Gnomad FIN exome AF: 0.000766

Gnomad NFE exome AF: 0.000400

Gnomad OTH exome AF: 0.000895

GnomAD4 exome AF: 0.000476 AC: 517 AN: 1086335 Hom.: 15 Cov.: 32 AF XY: 0.000671 AC XY: 237 AN XY: 352999

Gnomad4 AFR exome AF: 0.0000384

Gnomad4 AMR exome AF: 0.00111

Gnomad4 ASJ exome AF: 0.0000527

Gnomad4 EAS exome AF: 0.000999

Gnomad4 SAS exome AF: 0.000485

Gnomad4 FIN exome AF: 0.00227

Gnomad4 NFE exome AF: 0.000367

Gnomad4 OTH exome AF: 0.000461

GnomAD4 genome AF: 0.000320 AC: 34 AN: 106121 Hom.: 1 Cov.: 18 AF XY: 0.000166 AC XY: 5 AN XY: 30089

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000987

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000519

Gnomad4 NFE AF: 0.000344

Gnomad4 OTH AF: 0.00206

Alfa AF: 0.00123 Hom.: 12

ExAC AF: 0.000773 AC: 93

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

OPN1LW: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.0010
Dann	Benign	0.33
FATHMM_MKL	Benign	0.0047	N
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.023	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.24	N
REVEL	Benign	0.053
Sift	Benign	0.38	T
Sift4G	Benign	1.0	T
Vest4		0.044
MVP		0.043
MPC		0.88
ClinPred		0.0017	T
GERP RS		-0.091
gMVP		0.66

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

Other links and lift over

dbSNP: rs1065422; hg19: chrX-153416362; COSMIC: COSV100886919; COSMIC: COSV100886919;