rs12138459

Variant names:

• chr1-241560315-G-A
• rs12138459
• NM_003679.5:c.362-350G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-241560315-G-A
• chr1-241560315-G-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.362-350G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,072 control chromosomes in the GnomAD database, including 5,490 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 0.25 (5490 hom., cov: 32)
• Consequence: KMO NM_003679.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 5 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]

KMO Gene-Disease associations (from GenCC):

• pellagra

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMO	NM_003679.5	c.362-350G>A		intron_variant	Intron 5 of 14	ENST00000366559.9	NP_003670.2
KMO	NM_001410944.1	c.362-350G>A		intron_variant	Intron 5 of 14		NP_001397873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMO	ENST00000366559.9	c.362-350G>A		intron_variant	Intron 5 of 14	1	NM_003679.5	ENSP00000355517.4

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38677 AN: 151954 Hom.: 5486 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.266

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38680 AN: 152072 Hom.: 5490 Cov.: 32 AF XY: 0.256 AC XY: 19014 AN XY: 74322

African (AFR) AF: 0.124 AC: 5165 AN: 41494

American (AMR) AF: 0.247 AC: 3774 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1210 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1590 AN: 5146

South Asian (SAS) AF: 0.326 AC: 1574 AN: 4826

European-Finnish (FIN) AF: 0.300 AC: 3166 AN: 10566

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.314 AC: 21348 AN: 67986

Other (OTH) AF: 0.270 AC: 571 AN: 2116

Alfa AF: 0.276 Hom.: 7603

Bravo AF: 0.241

Asia WGS AF: 0.348 AC: 1206 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.6
DANN	Benign	0.84
PhyloP100		0.17
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: rs12138459; hg19: chr1-241723615;