rs1053221

Positions:

• chr1-241592265-T-C

Variant summary

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

The NM_003679.5(KMO):​c.*112T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 753,726 control chromosomes in the GnomAD database, including 10,531 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 0.13 (1556 hom., cov: 31)
  • Exomes 𝑓: 0.17 (8975 hom.)
• Consequence: KMO NM_003679.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.711

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KMO	NM_003679.5	c.*112T>C		3_prime_UTR_variant	15/15	ENST00000366559.9	NP_003670.2
KMO	NM_001410944.1	c.*112T>C		3_prime_UTR_variant	15/15		NP_001397873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KMO	ENST00000366559.9	c.*112T>C		3_prime_UTR_variant	15/15	1	NM_003679.5	ENSP00000355517.4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19570 AN: 152060 Hom.: 1553 Cov.: 31

Gnomad AFR AF: 0.0331

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.133

GnomAD4 exome AF: 0.166 AC: 99872 AN: 601548 Hom.: 8975 Cov.: 8 AF XY: 0.167 AC XY: 52791 AN XY: 315852

Gnomad4 AFR exome AF: 0.0296

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.184

Gnomad4 EAS exome AF: 0.224

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.159

GnomAD4 genome AF: 0.129 AC: 19578 AN: 152178 Hom.: 1556 Cov.: 31 AF XY: 0.130 AC XY: 9659 AN XY: 74402

Gnomad4 AFR AF: 0.0330

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.138

Alfa AF: 0.161 Hom.: 3591

Bravo AF: 0.120

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.85

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

Publications

LitVar

Other links and lift over

dbSNP: rs1053221; hg19: chr1-241755567; COSMIC: COSV59366901; COSMIC: COSV59366901;