X-154154684-T-C

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.689T>C(p.Ile230Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00296 in 1,188,737 control chromosomes in the GnomAD database, including 10 homozygotes. There are 191 hemizygotes in GnomAD. In-silico tool predicts 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 0.0024 (0 hom., 9 hem., cov: 17)
  • Exomes 𝑓: 0.0030 (10 hom. 182 hem.)
• Consequence: OPN1LW NM_020061.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.06

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=0.016978055).
• BP6: Variant X-154154684-T-C is Benign according to our data. Variant chrX-154154684-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661787.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154154684-T-C is described in Lovd as [Benign].
• BS2: High Hemizygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1LW	NM_020061.6	c.689T>C	p.Ile230Thr	missense_variant	4/6	ENST00000369951.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1LW	ENST00000369951.9	c.689T>C	p.Ile230Thr	missense_variant	4/6	1	NM_020061.6	P1
OPN1LW	ENST00000442922.1	c.278T>C	p.Ile93Thr	missense_variant	2/4	5
OPN1LW	ENST00000463296.1	n.588+1576T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.00244 AC: 260 AN: 106704 Hom.: 0 Cov.: 17 AF XY: 0.000303 AC XY: 9 AN XY: 29692

Gnomad AFR AF: 0.00105

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00104

Gnomad ASJ AF: 0.00396

Gnomad EAS AF: 0.000589

Gnomad SAS AF: 0.000830

Gnomad FIN AF: 0.000728

Gnomad MID AF: 0.00429

Gnomad NFE AF: 0.00388

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00232 AC: 418 AN: 180224 Hom.: 3 AF XY: 0.000461 AC XY: 30 AN XY: 65072

Gnomad AFR exome AF: 0.00107

Gnomad AMR exome AF: 0.00146

Gnomad ASJ exome AF: 0.00234

Gnomad EAS exome AF: 0.000946

Gnomad SAS exome AF: 0.000907

Gnomad FIN exome AF: 0.000954

Gnomad NFE exome AF: 0.00362

Gnomad OTH exome AF: 0.00269

GnomAD4 exome AF: 0.00301 AC: 3253 AN: 1081981 Hom.: 10 Cov.: 31 AF XY: 0.000522 AC XY: 182 AN XY: 348799

Gnomad4 AFR exome AF: 0.000914

Gnomad4 AMR exome AF: 0.00160

Gnomad4 ASJ exome AF: 0.00281

Gnomad4 EAS exome AF: 0.00174

Gnomad4 SAS exome AF: 0.00126

Gnomad4 FIN exome AF: 0.00156

Gnomad4 NFE exome AF: 0.00336

Gnomad4 OTH exome AF: 0.00295

GnomAD4 genome AF: 0.00244 AC: 260 AN: 106756 Hom.: 0 Cov.: 17 AF XY: 0.000302 AC XY: 9 AN XY: 29754

Gnomad4 AFR AF: 0.00105

Gnomad4 AMR AF: 0.00104

Gnomad4 ASJ AF: 0.00396

Gnomad4 EAS AF: 0.000591

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.000728

Gnomad4 NFE AF: 0.00388

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00292 Hom.: 6

ESP6500AA AF: 0.000786 AC: 3

ESP6500EA AF: 0.00285 AC: 19

ExAC AF: 0.00291 AC: 350

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

Oct 01, 2023

OPN1LW: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	4.3
Dann	Benign	0.70
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.017	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.90	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Benign	0.13
Sift	Benign	0.094	T;D
Sift4G	Benign	0.12	T;T
Vest4		0.12
MVP		0.47
MPC		0.90
ClinPred		0.016	T
GERP RS		1.8
gMVP		0.73

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: rs148583295; hg19: chrX-153420159; COSMIC: COSV64049257; COSMIC: COSV64049257;