Variant X-154193621-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_000513.2(OPN1MW):c.958G>A(p.Val320Ile) 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: 𝑓 0.000038 ( 0 hom., 0 hem., cov: 13)

Exomes 𝑓: 0.000015 ( 0 hom. 3 hem. )

Failed GnomAD Quality Control

Consequence

OPN1MW
NM_000513.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.130

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07365611).

BP6

Variant X-154193621-G-A is Benign according to our data. Variant chrX-154193621-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2237824.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW	NM_000513.2 linkuse as main transcript	c.958G>A	p.Val320Ile	missense_variant	5/6	ENST00000595290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW	ENST00000595290.6 linkuse as main transcript	c.958G>A	p.Val320Ile	missense_variant	5/6	1	NM_000513.2	P1
OPN1MW	ENST00000596998.2 linkuse as main transcript	c.382+163G>A		intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

78844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

17882

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000689

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000143

AC:

AN:

140268

Hom.:

AF XY:

0.0000227

AC XY:

AN XY:

43994

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000312

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000146

AC:

AN:

960490

Hom.:

Cov.:

AF XY:

0.0000108

AC XY:

AN XY:

278400

show subpopulations

Gnomad4 AFR exome

AF:

0.0000533

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000176

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000380

AC:

AN:

78844

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

17882

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000689

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000101

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 15, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.92

Cadd

Benign

0.79

Dann

Benign

0.81

DEOGEN2

Benign

0.035

FATHMM_MKL

Benign

0.032

M_CAP

Benign

0.0022

MetaRNN

Benign

0.074

MetaSVM

Benign

-0.96

MutationTaster

Benign

1.0

PrimateAI

Benign

0.43

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.14

MutPred

0.39

Loss of catalytic residue at V320 (P = 0.1154);

MVP

0.13

ClinPred

0.052

GERP RS

0.22

Varity_R

0.055

gMVP

0.088

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over