X-154187964-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.307A>G(p.Thr103Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (2 hom., 3 hem., cov: 3)
  • Exomes 𝑓: 0.0054 (73 hom. 148 hem.)
  • Failed GnomAD Quality Control
• Consequence: OPN1MW NM_000513.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.83

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=0.0038114786).
• BP6: Variant X-154187964-A-G is Benign according to our data. Variant chrX-154187964-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2661789.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154187964-A-G is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW	NM_000513.2	c.307A>G	p.Thr103Ala	missense_variant	2/6	ENST00000595290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW	ENST00000595290.6	c.307A>G	p.Thr103Ala	missense_variant	2/6	1	NM_000513.2	P1
OPN1MW	ENST00000595330.1	n.317A>G		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 206 AN: 31066 Hom.: 2 Cov.: 3 AF XY: 0.000679 AC XY: 3 AN XY: 4416 FAILED QC

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.00126

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00727

Gnomad OTH AF: 0.00641

GnomAD3 exomes AF: 0.00558 AC: 330 AN: 59187 Hom.: 6 AF XY: 0.000747 AC XY: 10 AN XY: 13385

Gnomad AFR exome AF: 0.00326

Gnomad AMR exome AF: 0.00608

Gnomad ASJ exome AF: 0.0177

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00316

Gnomad NFE exome AF: 0.00679

Gnomad OTH exome AF: 0.00506

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00542 AC: 3690 AN: 680657 Hom.: 73 Cov.: 12 AF XY: 0.000829 AC XY: 148 AN XY: 178503

Gnomad4 AFR exome AF: 0.00185

Gnomad4 AMR exome AF: 0.00370

Gnomad4 ASJ exome AF: 0.0157

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000175

Gnomad4 FIN exome AF: 0.00169

Gnomad4 NFE exome AF: 0.00587

Gnomad4 OTH exome AF: 0.00656

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00663 AC: 206 AN: 31053 Hom.: 2 Cov.: 3 AF XY: 0.000680 AC XY: 3 AN XY: 4415

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.0193

Gnomad4 EAS AF: 0.00127

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.00728

Gnomad4 OTH AF: 0.00639

Alfa AF: 0.00449 Hom.: 14

ExAC AF: 0.00404 AC: 297

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

Feb 01, 2024

OPN1MW: PP2, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	20
Dann	Benign	0.93
DEOGEN2	Benign	0.055	T
FATHMM_MKL	Uncertain	0.83	D
MetaRNN	Benign	0.0038	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.60	T
Sift4G	Benign	0.36	T
Polyphen		0.17	B
Vest4		0.097
MVP		0.95
ClinPred		0.0099	T
GERP RS		2.9
Varity_R		0.26
gMVP		0.71

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: rs781807082; hg19: chrX-153453453;