X-154153062-A-T

Variant names:

• chrX-154153062-A-T
• rs145009674
• NM_020061.6:c.532A>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_020061.6(OPN1LW):​c.532A>T​(p.Ile178Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I178V) has been classified as Benign.

• Frequency: Genomes: not found (cov: 0)
• Consequence: OPN1LW NM_020061.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.68
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• blue cone monochromacy

  Inheritance: XL Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, G2P
• red color blindness

  Inheritance: XL Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• cone-rod dystrophy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.30679715).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020061.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN1LW	NM_020061.6	MANE Select	c.532A>T	p.Ile178Phe	missense	Exon 3 of 6	NP_064445.2	P04000

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN1LW	ENST00000369951.9	TSL:1 MANE Select	c.532A>T	p.Ile178Phe	missense	Exon 3 of 6	ENSP00000358967.4	P04000
	OPN1LW	ENST00000442922.1	TSL:5	c.121A>T	p.Ile41Phe	missense	Exon 1 of 4	ENSP00000402493.1	H0Y622
	OPN1LW	ENST00000463296.1	TSL:5	n.542A>T		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.0070
DANN	Benign	0.84
FATHMM_MKL	Benign	0.072	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-1.1	T
PhyloP100		-2.7
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.15
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.21	T
Vest4		0.29
MutPred		0.65		Gain of catalytic residue at I178 (P = 0.1098)
MVP		0.81
MPC		1.4
ClinPred		0.24	T
GERP RS		-5.9
PromoterAI		-0.029	Neutral
gMVP		0.89
Mutation Taster		=81/19	polymorphism

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: rs145009674; hg19: chrX-153418535;