X-154193498-T-G

Position:

chrX-154193498-T-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000513.2(OPN1MW):c.835T>G(p.Phe279Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00045 in 944,760 control chromosomes in the GnomAD database, including 38 homozygotes. There are 165 hemizygotes in GnomAD. 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 0.00027 ( 2 hom., 7 hem., cov: 14)

Exomes 𝑓: 0.00045 ( 38 hom. 165 hem. )

Failed GnomAD Quality Control

Consequence

OPN1MW
NM_000513.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.55

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:

OPN1MW (HGNC:):

OPN1MW links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016135067).

BP6

Variant X-154193498-T-G is Benign according to our data. Variant chrX-154193498-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 3204387.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154193498-T-G is described in Lovd as [Likely_benign].

BS2

High Homozygotes in GnomAdExome4 at 38 Mitochondrial gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
OPN1MW	NM_000513.2 linkuse as main transcript	c.835T>G	p.Phe279Val	missense_variant	5/6	ENST00000595290.6	NP_000504.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
OPN1MW	ENST00000595290.6 linkuse as main transcript	c.835T>G	p.Phe279Val	missense_variant	5/6	1	NM_000513.2	ENSP00000472316.1	P04001
OPN1MW	ENST00000596998.2 linkuse as main transcript	c.381+40T>G		intron_variant		5		ENSP00000469055.1	H0Y642
OPN1MW	ENST00000595330.1 linkuse as main transcript	n.679T>G		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes

AF:

0.000266

AC:

AN:

82715

Hom.:

Cov.:

AF XY:

0.000339

AC XY:

AN XY:

20669

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00975

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000972

AC:

149

AN:

153266

Hom.:

AF XY:

0.00120

AC XY:

AN XY:

50030

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.0000968

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00854

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000450

AC:

425

AN:

944760

Hom.:

Cov.:

AF XY:

0.000614

AC XY:

165

AN XY:

268750

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000752

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00824

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000164

Gnomad4 OTH exome

AF:

0.000532

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000266

AC:

AN:

82685

Hom.:

Cov.:

AF XY:

0.000338

AC XY:

AN XY:

20681

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000137

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00977

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

ExAC

AF:

0.00114

AC:

122

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

Sep 23, 2023

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

-0.80

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.0040

DANN

Benign

0.46

DEOGEN2

Benign

0.037

FATHMM_MKL

Benign

0.0094

M_CAP

Benign

0.0021

MetaRNN

Benign

0.016

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.43

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.055

MutPred

0.44

Loss of stability (P = 0.2533);

MVP

0.10

ClinPred

0.0024

GERP RS

-0.95

Varity_R

0.056

gMVP

0.19

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