Variant X-154154701-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_020061.6(OPN1LW):c.706A>C(p.Met236Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000665 in 1,189,711 control chromosomes in the GnomAD database, including 14 homozygotes. There are 238 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 (★).

Frequency

Genomes: 𝑓 0.00096 ( 0 hom., 21 hem., cov: 18)

Exomes 𝑓: 0.00064 ( 14 hom. 217 hem. )

Consequence

OPN1LW
NM_020061.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.53

Variant links:

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]

OPN1LW links:

OPN1LW (HGNC:):

OPN1LW links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0092149675).

BP6

Variant X-154154701-A-C is Benign according to our data. Variant chrX-154154701-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661788.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 21 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1LW	NM_020061.6 linkuse as main transcript	c.706A>C	p.Met236Leu	missense_variant	4/6	ENST00000369951.9	NP_064445.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OPN1LW	ENST00000369951.9 linkuse as main transcript	c.706A>C	p.Met236Leu	missense_variant	4/6	1	NM_020061.6	ENSP00000358967.4	P04000
OPN1LW	ENST00000442922.1 linkuse as main transcript	c.295A>C	p.Met99Leu	missense_variant	2/4	5		ENSP00000402493.1	H0Y622
OPN1LW	ENST00000463296.1 linkuse as main transcript	n.588+1593A>C		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.000960

AC:

102

AN:

106263

Hom.:

Cov.:

AF XY:

0.000681

AC XY:

AN XY:

29379

show subpopulations

Gnomad AFR

AF:

0.00199

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000104

Gnomad ASJ

AF:

0.00119

Gnomad EAS

AF:

0.000590

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000680

Gnomad OTH

AF:

0.000704

GnomAD3 exomes

AF:

0.000572

AC:

103

AN:

180186

Hom.:

AF XY:

0.000400

AC XY:

AN XY:

65046

show subpopulations

Gnomad AFR exome

AF:

0.00223

Gnomad AMR exome

AF:

0.000149

Gnomad ASJ exome

AF:

0.00151

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.000160

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000597

Gnomad OTH exome

AF:

0.00112

GnomAD4 exome

AF:

0.000636

AC:

689

AN:

1083398

Hom.:

Cov.:

AF XY:

0.000620

AC XY:

217

AN XY:

350096

show subpopulations

Gnomad4 AFR exome

AF:

0.00213

Gnomad4 AMR exome

AF:

0.000349

Gnomad4 ASJ exome

AF:

0.00169

Gnomad4 EAS exome

AF:

0.0000668

Gnomad4 SAS exome

AF:

0.000150

Gnomad4 FIN exome

AF:

0.0000251

Gnomad4 NFE exome

AF:

0.000663

Gnomad4 OTH exome

AF:

0.000571

GnomAD4 genome

AF:

0.000959

AC:

102

AN:

106313

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

AN XY:

29437

show subpopulations

Gnomad4 AFR

AF:

0.00199

Gnomad4 AMR

AF:

0.000104

Gnomad4 ASJ

AF:

0.00119

Gnomad4 EAS

AF:

0.000592

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000680

Gnomad4 OTH

AF:

0.000695

Alfa

AF:

0.0167

Hom.:

481

ExAC

AF:

0.000608

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

OPN1LW: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.083

DANN

Benign

0.60

FATHMM_MKL

Benign

0.055

LIST_S2

Benign

0.72

.;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.0092

T;T

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.47

N;N

REVEL

Benign

0.044

Sift

Benign

0.083

T;T

Sift4G

Benign

0.34

T;T

Vest4

0.078

MutPred

0.39

Loss of catalytic residue at M236 (P = 0.0177);.;

MVP

0.28

MPC

0.64

ClinPred

0.00069

GERP RS

-3.0

gMVP

0.51

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over