1-241594687-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_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

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.43

Publications

5 publications found

Variant links:

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]

OPN3 links:

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]

KMO Gene-Disease associations (from GenCC):

pellagra
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

KMO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -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 VariationId is 2640207.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014322.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OPN3	NM_014322.3	MANE Select	c.950G>A	p.Arg317Gln	missense	Exon 4 of 4	NP_055137.2	Q9H1Y3-1
KMO	NM_003679.5	MANE Select	c.*2534C>T		3_prime_UTR	Exon 15 of 15	NP_003670.2	O15229-1
KMO	NM_001410944.1		c.*2534C>T		3_prime_UTR	Exon 15 of 15	NP_001397873.1	O15229-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
OPN3	ENST00000366554.3	TSL:1 MANE Select	c.950G>A	p.Arg317Gln	missense	Exon 4 of 4	ENSP00000355512.2	Q9H1Y3-1
KMO	ENST00000366559.9	TSL:1 MANE Select	c.*2534C>T		3_prime_UTR	Exon 15 of 15	ENSP00000355517.4	O15229-1
OPN3	ENST00000469376.5	TSL:1	n.*220G>A		non_coding_transcript_exon	Exon 4 of 4	ENSP00000490012.1	Q6P5W7

Frequencies

GnomAD3 genomes

AF:

0.000671

AC:

102

AN:

152040

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.000695

AC:

172

AN:

247368

AF XY:

0.000739

show subpopulations

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 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.:

Cov.:

AF XY:

0.00120

AC XY:

869

AN XY:

725706

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33360

American (AMR)

AF:

0.000248

AC:

AN:

44302

Ashkenazi Jewish (ASJ)

AF:

0.0000384

AC:

AN:

26012

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.00106

AC:

AN:

85734

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5742

European-Non Finnish (NFE)

AF:

0.00145

AC:

1616

AN:

1110848

Other (OTH)

AF:

0.000946

AC:

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

178

268

357

446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

148

222

296

370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000677

AC:

103

AN:

152158

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41492

American (AMR)

AF:

0.000131

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00208

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000945

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00124

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00102

Hom.:

Bravo

AF:

0.000650

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000585

AC:

EpiCase

AF:

0.000928

EpiControl

AF:

0.00131

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Uncertain

-0.080

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.020

MetaRNN

Benign

0.14

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.0

PhyloP100

2.4

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.86

REVEL

Benign

0.28

Sift

Benign

0.25

Sift4G

Uncertain

0.013

Polyphen

1.0

Vest4

0.78

MVP

0.79

MPC

1.1

ClinPred

0.073

GERP RS

2.2

Varity_R

0.11

gMVP

0.89

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over