rs1053183

Positions:

• chr1-241595329-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003679.5(KMO):​c.*3176A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,154 control chromosomes in the GnomAD database, including 6,228 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6223 hom., cov: 32)
  • Exomes 𝑓: 0.23 (5 hom.)
• Consequence: KMO NM_003679.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

Genes affected

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]

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KMO	NM_003679.5	c.*3176A>G		3_prime_UTR_variant	15/15	ENST00000366559.9
OPN3	NM_014322.3	c.946-638T>C		intron_variant		ENST00000366554.3
KMO	NM_001410944.1	c.*3176A>G		3_prime_UTR_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMO	ENST00000366559.9	c.*3176A>G		3_prime_UTR_variant	15/15	1	NM_003679.5	P2
OPN3	ENST00000366554.3	c.946-638T>C		intron_variant		1	NM_014322.3	P1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42338 AN: 151944 Hom.: 6211 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.237

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.228 AC: 21 AN: 92 Hom.: 5 Cov.: 0 AF XY: 0.161 AC XY: 9 AN XY: 56

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.244

GnomAD4 genome AF: 0.279 AC: 42377 AN: 152062 Hom.: 6223 Cov.: 32 AF XY: 0.280 AC XY: 20835 AN XY: 74316

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.362

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.268

Alfa AF: 0.244 Hom.: 8020

Bravo AF: 0.298

Asia WGS AF: 0.381 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1053183; hg19: chr1-241758631;