X-154188004-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000513.2(OPN1MW):c.347A>C(p.Tyr116Ser) 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 0.0034 (22 hom., 13 hem., cov: 5)
  • Exomes 𝑓: 0.0018 (172 hom. 324 hem.)
  • Failed GnomAD Quality Control
• Consequence: OPN1MW NM_000513.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.010365188).
• BP6: Variant X-154188004-A-C is Benign according to our data. Variant chrX-154188004-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2457219.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-154188004-A-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00181 (1388/765562) while in subpopulation AFR AF= 0.0219 (150/6861). AF 95% confidence interval is 0.019. There are 172 homozygotes in gnomad4_exome. There are 324 alleles in male gnomad4_exome subpopulation. Median coverage is 16. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 46 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN1MW	NM_000513.2	c.347A>C	p.Tyr116Ser	missense_variant	2/6	ENST00000595290.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN1MW	ENST00000595290.6	c.347A>C	p.Tyr116Ser	missense_variant	2/6	1	NM_000513.2	P1
OPN1MW	ENST00000595330.1	n.357A>C		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 176 AN: 51146 Hom.: 22 Cov.: 5 AF XY: 0.00131 AC XY: 13 AN XY: 9938 FAILED QC

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00350

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00191

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00134

Gnomad MID AF: 0.00855

Gnomad NFE AF: 0.00165

Gnomad OTH AF: 0.00803

GnomAD3 exomes AF: 0.00209 AC: 183 AN: 87714 Hom.: 46 AF XY: 0.00121 AC XY: 28 AN XY: 23060

Gnomad AFR exome AF: 0.0299

Gnomad AMR exome AF: 0.00317

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000833

Gnomad SAS exome AF: 0.00114

Gnomad FIN exome AF: 0.000204

Gnomad NFE exome AF: 0.00115

Gnomad OTH exome AF: 0.00124

GnomAD4 exome AF: 0.00181 AC: 1388 AN: 765562 Hom.: 172 Cov.: 16 AF XY: 0.00156 AC XY: 324 AN XY: 207052

Gnomad4 AFR exome AF: 0.0219

Gnomad4 AMR exome AF: 0.00284

Gnomad4 ASJ exome AF: 0.0000696

Gnomad4 EAS exome AF: 0.000578

Gnomad4 SAS exome AF: 0.00108

Gnomad4 FIN exome AF: 0.000765

Gnomad4 NFE exome AF: 0.00168

Gnomad4 OTH exome AF: 0.00266

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00344 AC: 176 AN: 51121 Hom.: 22 Cov.: 5 AF XY: 0.00131 AC XY: 13 AN XY: 9943

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.00349

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00191

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00134

Gnomad4 NFE AF: 0.00165

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00595 Hom.: 24

ExAC AF: 0.00120 AC: 93

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

Feb 16, 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	-0.49	T
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.015
Dann	Benign	0.37
DEOGEN2	Benign	0.062	T
FATHMM_MKL	Benign	0.071	N
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.010	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	0.97	N
PrimateAI	Benign	0.46	T
Sift4G	Benign	0.41	T
Polyphen		0.0020	B
Vest4		0.041
MVP		0.10
ClinPred		0.0020	T
GERP RS		-2.4
Varity_R		0.092
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs201569525; hg19: chrX-153453493;