X-154190176-A-G

Variant summary

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

The NM_000513.2(OPN1MW):c.532A>G(p.Ile178Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Failed GnomAD Quality Control
• Consequence: OPN1MW NM_000513.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.27

Genes affected

OPN1MW (HGNC:4206): (opsin 1, medium wave sensitive) This gene encodes for a light absorbing visual pigment of the opsin gene family. The encoded protein is called green cone photopigment or medium-wavelength sensitive opsin. Opsins are G-protein coupled receptors with seven transmembrane domains, an N-terminal extracellular domain, and a C-terminal cytoplasmic domain. The long-wavelength opsin gene and multiple copies of 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 deutanopic colorblindness. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0038502216).
• BP6: Variant X-154190176-A-G is Benign according to our data. Variant chrX-154190176-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3025002.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 38 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW	NM_000513.2	c.532A>G	p.Ile178Val	missense_variant	3/6	ENST00000595290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW	ENST00000595290.6	c.532A>G	p.Ile178Val	missense_variant	3/6	1	NM_000513.2	P1
OPN1MW	ENST00000596998.2	c.121A>G	p.Ile41Val	missense_variant	1/4	5
OPN1MW	ENST00000595330.1	n.542A>G		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0181 AC: 167 AN: 9233 Hom.: 38 AF XY: 0.0142 AC XY: 26 AN XY: 1831

Gnomad AFR exome AF: 0.351

Gnomad AMR exome AF: 0.0148

Gnomad ASJ exome AF: 0.0155

Gnomad EAS exome AF: 0.00247

Gnomad SAS exome AF: 0.00654

Gnomad FIN exome AF: 0.0368

Gnomad NFE exome AF: 0.00412

Gnomad OTH exome AF: 0.0218

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: 0.0632 Hom.: 119

ExAC AF: 0.0222 AC: 20

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

Jan 01, 2024

OPN1MW: PP2, BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.0020
Dann	Benign	0.20
DEOGEN2	Benign	0.040	T
FATHMM_MKL	Benign	0.017	N
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.0039	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.018
ClinPred		0.0016	T
GERP RS		-3.9
Varity_R		0.041
gMVP		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs375538821; hg19: chrX-153455665; COSMIC: COSV64039693;