1-241592265-T-C

Variant names:

• chr1-241592265-T-C
• rs1053221
• NM_003679.5:c.*112T>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: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=-0.78).
• 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 rank	MANE	Protein	UniProt
KMO	NM_003679.5	c.*112T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000366559.9	NP_003670.2
KMO	NM_001410944.1	c.*112T>C		3_prime_UTR_variant	Exon 15 of 15		NP_001397873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMO	ENST00000366559.9	c.*112T>C		3_prime_UTR_variant	Exon 15 of 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;