X-154190165-C-T

Position:

• chrX-154190165-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000513.2(OPN1MW):​c.521C>T​(p.Ala174Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/15 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: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.157

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]

OPN1MW (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008038938).
• BP6: Variant X-154190165-C-T is Benign according to our data. Variant chrX-154190165-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1174925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1MW	NM_000513.2	c.521C>T	p.Ala174Val	missense_variant	3/6	ENST00000595290.6	NP_000504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
OPN1MW	ENST00000595290.6	c.521C>T	p.Ala174Val	missense_variant	3/6	1	NM_000513.2	ENSP00000472316.1
OPN1MW	ENST00000596998.2	c.107C>T	p.Ala36Val	missense_variant	1/4	5		ENSP00000469055.1
OPN1MW	ENST00000595330.1	n.531C>T		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0238 AC: 232 AN: 9760 Hom.: 56 AF XY: 0.0200 AC XY: 39 AN XY: 1954

Gnomad AFR exome AF: 0.402

Gnomad AMR exome AF: 0.00901

Gnomad ASJ exome AF: 0.0264

Gnomad EAS exome AF: 0.0193

Gnomad SAS exome AF: 0.00858

Gnomad FIN exome AF: 0.0437

Gnomad NFE exome AF: 0.00587

Gnomad OTH exome AF: 0.0323

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: 0.0877 Hom.: 167

ExAC AF: 0.0246 AC: 38

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	OPN1MW: PP2, BP4, BS2 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.012
DANN	Benign	0.19
DEOGEN2	Benign	0.068	T
FATHMM_MKL	Benign	0.021	N
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-0.93	T
PrimateAI	Benign	0.43	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.071
ClinPred		0.00018	T
GERP RS		-1.8
Varity_R		0.027
gMVP		0.37

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: rs372044027; hg19: chrX-153455654; COSMIC: COSV64039691;