rs1053183

Variant names:

• chr1-241595329-A-G
• rs1053183
• NM_003679.5:c.*3176A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003679.5. 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
	KMO	NM_003679.5	MANE Select	c.*3176A>G		3_prime_UTR	Exon 15 of 15	NP_003670.2	O15229-1
	OPN3	NM_014322.3	MANE Select	c.946-638T>C		intron	N/A	NP_055137.2	Q9H1Y3-1
	KMO	NM_001410944.1		c.*3176A>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
	KMO	ENST00000366559.9	TSL:1 MANE Select	c.*3176A>G		3_prime_UTR	Exon 15 of 15	ENSP00000355517.4	O15229-1
	OPN3	ENST00000366554.3	TSL:1 MANE Select	c.946-638T>C		intron	N/A	ENSP00000355512.2	Q9H1Y3-1
	OPN3	ENST00000469376.5	TSL:1	n.*216-638T>C		intron	N/A	ENSP00000490012.1	Q6P5W7

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

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.244 AC: 20 AN: 82

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.337 AC: 13964 AN: 41454

American (AMR) AF: 0.362 AC: 5530 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 908 AN: 3472

East Asian (EAS) AF: 0.423 AC: 2182 AN: 5156

South Asian (SAS) AF: 0.287 AC: 1386 AN: 4826

European-Finnish (FIN) AF: 0.187 AC: 1984 AN: 10590

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15567 AN: 67986

Other (OTH) AF: 0.268 AC: 567 AN: 2112

Alfa AF: 0.253 Hom.: 14507

Bravo AF: 0.298

Asia WGS AF: 0.381 AC: 1321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.67
PhyloP100		0.0020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1053183; hg19: chr1-241758631;