1-241594586-C-G

Variant names:

• chr1-241594586-C-G
• NM_014322.3:c.1051G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014322.3(OPN3):​c.1051G>C​(p.Val351Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: OPN3 NM_014322.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.71
• Publications: 0 publications found

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]

KMO Gene-Disease associations (from GenCC):

• pellagra

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19902042).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN3	NM_014322.3	MANE Select	c.1051G>C	p.Val351Leu	missense	Exon 4 of 4	NP_055137.2	Q9H1Y3-1
	KMO	NM_003679.5	MANE Select	c.*2433C>G		3_prime_UTR	Exon 15 of 15	NP_003670.2	O15229-1
	KMO	NM_001410944.1		c.*2433C>G		3_prime_UTR	Exon 15 of 15	NP_001397873.1	O15229-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OPN3	ENST00000366554.3	TSL:1 MANE Select	c.1051G>C	p.Val351Leu	missense	Exon 4 of 4	ENSP00000355512.2	Q9H1Y3-1
	KMO	ENST00000366559.9	TSL:1 MANE Select	c.*2433C>G		3_prime_UTR	Exon 15 of 15	ENSP00000355517.4	O15229-1
	OPN3	ENST00000469376.5	TSL:1	n.*321G>C		non_coding_transcript_exon	Exon 4 of 4	ENSP00000490012.1	Q6P5W7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	0.0043	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.031	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.6	L
PhyloP100		5.7
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.43	N
REVEL	Benign	0.085
Sift	Benign	0.25	T
Sift4G	Uncertain	0.021	D
Polyphen		0.60	P
Vest4		0.36
MutPred		0.24		Loss of MoRF binding (P = 0.1141)
MVP		0.27
MPC		0.57
ClinPred		0.75	D
GERP RS		4.1
Varity_R		0.17
gMVP		0.48
Mutation Taster		=73/27	polymorphism

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

Other links and lift over

hg19: chr1-241757888;