1-241562310-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003679.5(KMO):​c.593C>G​(p.Thr198Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

KMO
NM_003679.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.45
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 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14306217).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KMONM_003679.5 linkc.593C>G p.Thr198Ser missense_variant 7/15 ENST00000366559.9 NP_003670.2 O15229-1A8K693
KMONM_001410944.1 linkc.593C>G p.Thr198Ser missense_variant 7/15 NP_001397873.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KMOENST00000366559.9 linkc.593C>G p.Thr198Ser missense_variant 7/151 NM_003679.5 ENSP00000355517.4 O15229-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 20, 2024The c.593C>G (p.T198S) alteration is located in exon 7 (coding exon 7) of the KMO gene. This alteration results from a C to G substitution at nucleotide position 593, causing the threonine (T) at amino acid position 198 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.096
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
14
DANN
Benign
0.89
DEOGEN2
Benign
0.0083
.;T;.
Eigen
Benign
-0.55
Eigen_PC
Benign
-0.46
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Benign
0.68
T;T;T
M_CAP
Benign
0.012
T
MetaRNN
Benign
0.14
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.1
L;L;L
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-1.1
N;N;N
REVEL
Benign
0.064
Sift
Benign
0.70
T;T;T
Sift4G
Benign
0.59
T;T;T
Polyphen
0.061
B;B;.
Vest4
0.28
MutPred
0.40
Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);Loss of sheet (P = 0.0315);
MVP
0.47
MPC
0.32
ClinPred
0.34
T
GERP RS
2.6
Varity_R
0.24
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1661877203; hg19: chr1-241725610; API