1-241594687-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Moderate BP6_Moderate

The NM_014322.3(OPN3):c.950G>A(p.Arg317Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,611,462 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00068 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: OPN3 NM_014322.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.43

Genes affected

OPN3 (HGNC:14007): (opsin 3) Opsins are members of the guanine nucleotide-binding protein (G protein)-coupled receptor superfamily. In addition to the visual opsins, mammals possess several photoreceptive non-visual opsins that are expressed in extraocular tissues. This gene, opsin 3, is strongly expressed in brain and testis and weakly expressed in liver, placenta, heart, lung, skeletal muscle, kidney, and pancreas. The gene may also be expressed in the retina. The protein has the canonical features of a photoreceptive opsin protein. [provided by RefSeq, Jul 2008]

KMO (HGNC:6381): (kynurenine 3-monooxygenase) This gene encodes a mitochondrion outer membrane protein that catalyzes the hydroxylation of L-tryptophan metabolite, L-kynurenine, to form L-3-hydroxykynurenine. Studies in yeast identified this gene as a therapeutic target for Huntington disease. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13554418).
• BP6: Variant 1-241594687-C-T is Benign according to our data. Variant chr1-241594687-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2640207.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
OPN3	NM_014322.3	c.950G>A	p.Arg317Gln	missense_variant	4/4	ENST00000366554.3
KMO	NM_003679.5	c.*2534C>T		3_prime_UTR_variant	15/15	ENST00000366559.9
KMO	NM_001410944.1	c.*2534C>T		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
OPN3	ENST00000366554.3	c.950G>A	p.Arg317Gln	missense_variant	4/4	1	NM_014322.3	P1
KMO	ENST00000366559.9	c.*2534C>T		3_prime_UTR_variant	15/15	1	NM_003679.5	P2

Frequencies

GnomAD3 genomes AF: 0.000671 AC: 102 AN: 152040 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000695 AC: 172 AN: 247368 Hom.: 1 AF XY: 0.000739 AC XY: 99 AN XY: 133884

Gnomad AFR exome AF: 0.000190

Gnomad AMR exome AF: 0.000263

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00126

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00104

Gnomad OTH exome AF: 0.000833

GnomAD4 exome AF: 0.00122 AC: 1782 AN: 1459304 Hom.: 1 Cov.: 31 AF XY: 0.00120 AC XY: 869 AN XY: 725706

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000248

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00106

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.00145

Gnomad4 OTH exome AF: 0.000946

GnomAD4 genome AF: 0.000677 AC: 103 AN: 152158 Hom.: 1 Cov.: 33 AF XY: 0.000699 AC XY: 52 AN XY: 74388

Gnomad4 AFR AF: 0.000145

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00208

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.00124

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.000650

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000585 AC: 71

EpiCase AF: 0.000928

EpiControl AF: 0.00131

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

OPN3: BP4 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Uncertain	-0.080
Cadd	Uncertain	24
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.0	M
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.86	N
REVEL	Benign	0.28
Sift	Benign	0.25	T
Sift4G	Uncertain	0.013	D
Polyphen		1.0	D
Vest4		0.78
MVP		0.79
MPC		1.1
ClinPred		0.073	T
GERP RS		2.2
Varity_R		0.11
gMVP		0.89

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: rs138406816; hg19: chr1-241757989; COSMIC: COSV59362622; COSMIC: COSV59362622;