rs1662085367

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003679.5(KMO):​c.721T>C​(p.Phe241Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F241V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

KMO
NM_003679.5 missense

Scores

4
7
8

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.96
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KMONM_003679.5 linkc.721T>C p.Phe241Leu missense_variant Exon 9 of 15 ENST00000366559.9 NP_003670.2 O15229-1A8K693
KMONM_001410944.1 linkc.721T>C p.Phe241Leu missense_variant Exon 9 of 15 NP_001397873.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KMOENST00000366559.9 linkc.721T>C p.Phe241Leu missense_variant Exon 9 of 15 1 NM_003679.5 ENSP00000355517.4 O15229-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.81
BayesDel_addAF
Uncertain
0.066
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
.;T;.
Eigen
Uncertain
0.65
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.84
T;D;D
M_CAP
Benign
0.0091
T
MetaRNN
Uncertain
0.68
D;D;D
MetaSVM
Benign
-0.62
T
MutationAssessor
Uncertain
2.3
M;M;M
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-4.7
D;D;D
REVEL
Uncertain
0.30
Sift
Benign
0.057
T;T;T
Sift4G
Benign
0.096
T;T;T
Polyphen
0.86
P;P;.
Vest4
0.65
MutPred
0.52
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.66
MPC
0.88
ClinPred
0.99
D
GERP RS
5.9
Varity_R
0.79
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-241729824; API