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GeneBe

1-241566589-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003679.5(KMO):c.786G>A(p.Pro262=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,613,574 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0060 ( 6 hom., cov: 32)
Exomes 𝑓: 0.010 ( 103 hom. )

Consequence

KMO
NM_003679.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.845
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-241566589-G-A is Benign according to our data. Variant chr1-241566589-G-A is described in ClinVar as [Benign]. Clinvar id is 771693.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.845 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KMONM_003679.5 linkuse as main transcriptc.786G>A p.Pro262= synonymous_variant 9/15 ENST00000366559.9
KMONM_001410944.1 linkuse as main transcriptc.786G>A p.Pro262= synonymous_variant 9/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KMOENST00000366559.9 linkuse as main transcriptc.786G>A p.Pro262= synonymous_variant 9/151 NM_003679.5 P2O15229-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00603
AC:
917
AN:
152088
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00205
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00347
Gnomad ASJ
AF:
0.00289
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00189
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0109
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.00657
AC:
1649
AN:
251008
Hom.:
12
AF XY:
0.00644
AC XY:
874
AN XY:
135664
show subpopulations
Gnomad AFR exome
AF:
0.00203
Gnomad AMR exome
AF:
0.00467
Gnomad ASJ exome
AF:
0.00318
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000393
Gnomad FIN exome
AF:
0.00148
Gnomad NFE exome
AF:
0.0117
Gnomad OTH exome
AF:
0.00785
GnomAD4 exome
AF:
0.0104
AC:
15211
AN:
1461368
Hom.:
103
Cov.:
30
AF XY:
0.0102
AC XY:
7397
AN XY:
726996
show subpopulations
Gnomad4 AFR exome
AF:
0.00164
Gnomad4 AMR exome
AF:
0.00434
Gnomad4 ASJ exome
AF:
0.00260
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000348
Gnomad4 FIN exome
AF:
0.00182
Gnomad4 NFE exome
AF:
0.0129
Gnomad4 OTH exome
AF:
0.00641
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00602
AC:
917
AN:
152206
Hom.:
6
Cov.:
32
AF XY:
0.00547
AC XY:
407
AN XY:
74412
show subpopulations
Gnomad4 AFR
AF:
0.00205
Gnomad4 AMR
AF:
0.00347
Gnomad4 ASJ
AF:
0.00289
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000415
Gnomad4 FIN
AF:
0.00189
Gnomad4 NFE
AF:
0.0109
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.00943
Hom.:
1
Bravo
AF:
0.00654
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.0101
EpiControl
AF:
0.0107

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 28, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.49
Cadd
Benign
6.7
Dann
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: rs142152979; hg19: chr1-241729889; COSMIC: COSV63806393; COSMIC: COSV63806393; API