X-154190182-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_000513.2(OPN1MW):c.538G>T(p.Ala180Ser) 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 Benign (no stars).

• Frequency:
  • Genomes: not found (cov: 0)
  • Failed GnomAD Quality Control
• Consequence: OPN1MW NM_000513.2 missense
• Clinical Significance: Benign no assertion criteria provided B:2
• Conservation: PhyloP100: -3.98

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023262799).
• BP6: Variant X-154190182-G-T is Benign according to our data. Variant chrX-154190182-G-T is described in ClinVar as [Benign]. Clinvar id is 1284433.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chrX-154190182-G-T is described in Lovd as [Benign].
• BS2: High Homozygotes in GnomAdExome at 101 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW	NM_000513.2	c.538G>T	p.Ala180Ser	missense_variant	3/6	ENST00000595290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW	ENST00000595290.6	c.538G>T	p.Ala180Ser	missense_variant	3/6	1	NM_000513.2	P1
OPN1MW	ENST00000596998.2	c.127G>T	p.Ala43Ser	missense_variant	1/4	5
OPN1MW	ENST00000595330.1	n.548G>T		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD3 exomes AF: 0.0704 AC: 557 AN: 7917 Hom.: 101 AF XY: 0.0503 AC XY: 73 AN XY: 1451

Gnomad AFR exome AF: 0.207

Gnomad AMR exome AF: 0.175

Gnomad ASJ exome AF: 0.0857

Gnomad EAS exome AF: 0.0780

Gnomad SAS exome AF: 0.0434

Gnomad FIN exome AF: 0.0427

Gnomad NFE exome AF: 0.0322

Gnomad OTH exome AF: 0.0567

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: 0.0628 Hom.: 89

ExAC AF: 0.0181 AC: 11

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.0010
Dann	Benign	0.66
DEOGEN2	Benign	0.050	T
FATHMM_MKL	Benign	0.025	N
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.50	T
Sift4G	Benign	0.64	T
Polyphen		0.0020	B
Vest4		0.058
ClinPred		0.0028	T
GERP RS		-0.20
Varity_R		0.064
gMVP		0.59

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: rs949431; hg19: chrX-153455671; COSMIC: COSV64039719;