X-154193498-T-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.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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.55

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=0.016135067).
• 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 GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW	NM_000513.2	c.835T>G	p.Phe279Val	missense_variant	5/6	ENST00000595290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW	ENST00000595290.6	c.835T>G	p.Phe279Val	missense_variant	5/6	1	NM_000513.2	P1
OPN1MW	ENST00000596998.2	c.382+40T>G		intron_variant		5
OPN1MW	ENST00000595330.1	n.679T>G		non_coding_transcript_exon_variant	4/4	5

Frequencies

GnomAD3 genomes AF: 0.000266 AC: 22 AN: 82715 Hom.: 2 Cov.: 14 AF XY: 0.000339 AC XY: 7 AN XY: 20669

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.: 11 AF XY: 0.00120 AC XY: 60 AN XY: 50030

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.: 38 Cov.: 31 AF XY: 0.000614 AC XY: 165 AN XY: 268750

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: 22 AN: 82685 Hom.: 2 Cov.: 14 AF XY: 0.000338 AC XY: 7 AN XY: 20681

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.: 0

ExAC AF: 0.00114 AC: 122

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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	T
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.0040
Dann	Benign	0.46
DEOGEN2	Benign	0.037	T
FATHMM_MKL	Benign	0.0094	N
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.016	T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.43	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.44		Loss of stability (P = 0.2533);
MVP		0.10
ClinPred		0.0024	T
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

Other links and lift over

dbSNP: rs782251342; hg19: chrX-153458989;