1-241592265-T-C

Variant names:

• chr1-241592265-T-C
• rs1053221
• NM_003679.5:c.*112T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMO	NM_003679.5	MANE Select	c.*112T>C		3_prime_UTR	Exon 15 of 15	NP_003670.2
	KMO	NM_001410944.1		c.*112T>C		3_prime_UTR	Exon 15 of 15	NP_001397873.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMO	ENST00000366559.9	TSL:1 MANE Select	c.*112T>C		3_prime_UTR	Exon 15 of 15	ENSP00000355517.4
	KMO	ENST00000366558.7	TSL:1	c.*112T>C		3_prime_UTR	Exon 15 of 15	ENSP00000355516.3
	KMO	ENST00000366557.8	TSL:5	c.*112T>C		3_prime_UTR	Exon 14 of 14	ENSP00000355515.4

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

African (AFR) AF: 0.0296 AC: 471 AN: 15928

American (AMR) AF: 0.107 AC: 2883 AN: 26936

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 3013 AN: 16356

East Asian (EAS) AF: 0.224 AC: 7211 AN: 32196

South Asian (SAS) AF: 0.191 AC: 10033 AN: 52588

European-Finnish (FIN) AF: 0.168 AC: 5580 AN: 33204

Middle Eastern (MID) AF: 0.112 AC: 438 AN: 3912

European-Non Finnish (NFE) AF: 0.168 AC: 65204 AN: 388694

Other (OTH) AF: 0.159 AC: 5039 AN: 31734

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

African (AFR) AF: 0.0330 AC: 1370 AN: 41546

American (AMR) AF: 0.122 AC: 1867 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 641 AN: 3470

East Asian (EAS) AF: 0.222 AC: 1150 AN: 5180

South Asian (SAS) AF: 0.198 AC: 953 AN: 4816

European-Finnish (FIN) AF: 0.155 AC: 1638 AN: 10594

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11469 AN: 67988

Other (OTH) AF: 0.138 AC: 290 AN: 2102

Alfa AF: 0.152 Hom.: 5299

Bravo AF: 0.120

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.6
DANN	Benign	0.85
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

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