X-154153041-G-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_020061.6(OPN1LW):c.511G>A(p.Val171Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. V171V) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 0)
  • Failed GnomAD Quality Control
• Consequence: OPN1LW NM_020061.6 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.251

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024058819).
• BS2: High Homozygotes in GnomAdExome at 2399 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1LW	NM_020061.6	c.511G>A	p.Val171Met	missense_variant	3/6	ENST00000369951.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1LW	ENST00000369951.9	c.511G>A	p.Val171Met	missense_variant	3/6	1	NM_020061.6	P1
OPN1LW	ENST00000442922.1	c.100G>A	p.Val34Met	missense_variant	1/4	5
OPN1LW	ENST00000463296.1	n.521G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.135 AC: 22598 AN: 166800 Hom.: 2399 AF XY: 0.133 AC XY: 7365 AN XY: 55360

Gnomad AFR exome AF: 0.291

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.0948

Gnomad EAS exome AF: 0.129

Gnomad SAS exome AF: 0.295

Gnomad FIN exome AF: 0.0975

Gnomad NFE exome AF: 0.0776

Gnomad OTH exome AF: 0.111

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.164 Hom.: 378

ESP6500AA AF: 0.291 AC: 1109

ESP6500EA AF: 0.0769 AC: 490

ExAC AF: 0.137 AC: 15461

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cone monochromatism Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.63
Cadd	Benign	0.74
Dann	Benign	0.81
FATHMM_MKL	Benign	0.052	N
MetaRNN	Benign	0.0024	T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.43	T
PROVEAN	Benign	0.27	N;N
REVEL	Benign	0.13
Sift	Uncertain	0.015	D;D
Sift4G	Benign	1.0	T;T
Vest4		0.025
MPC		0.75
ClinPred		0.0058	T
GERP RS		-1.1
gMVP		0.50

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: rs5986963; hg19: chrX-153418514; COSMIC: COSV64063933;