Genetic Variant KMO:c.809+142C>T (chr1-241566754-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_003679.5(KMO):c.809+142C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 844,098 control chromosomes in the GnomAD database, including 41,845 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 0.28 ( 6392 hom., cov: 32)

Exomes 𝑓: 0.31 ( 35453 hom. )

Consequence

KMO
NM_003679.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.264

Publications

23 publications found

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]

KMO Gene-Disease associations (from GenCC):

pellagra
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

KMO links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KMO	NM_003679.5 link	c.809+142C>T		intron_variant	Intron 9 of 14	ENST00000366559.9	NP_003670.2	O15229-1A8K693
KMO	NM_001410944.1 link	c.809+142C>T		intron_variant	Intron 9 of 14		NP_001397873.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KMO	ENST00000366559.9 link	c.809+142C>T		intron_variant	Intron 9 of 14	1	NM_003679.5	ENSP00000355517.4		O15229-1

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42529

AN:

151952

Hom.:

6384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.176

Gnomad AMR

AF:

0.290

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.398

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.325

Gnomad OTH

AF:

0.288

GnomAD4 exome

AF:

0.314

AC:

217365

AN:

692028

Hom.:

35453

AF XY:

0.313

AC XY:

114290

AN XY:

364804

show subpopulations

African (AFR)

AF:

0.164

AC:

2683

AN:

16402

American (AMR)

AF:

0.255

AC:

6365

AN:

24986

Ashkenazi Jewish (ASJ)

AF:

0.347

AC:

6575

AN:

18956

East Asian (EAS)

AF:

0.392

AC:

12496

AN:

31918

South Asian (SAS)

AF:

0.257

AC:

15179

AN:

59176

European-Finnish (FIN)

AF:

0.353

AC:

12785

AN:

36210

Middle Eastern (MID)

AF:

0.303

AC:

1115

AN:

3674

European-Non Finnish (NFE)

AF:

0.320

AC:

149456

AN:

466586

Other (OTH)

AF:

0.314

AC:

10711

AN:

34120

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

7251

14502

21753

29004

36255

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2804

5608

8412

11216

14020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.280

AC:

42557

AN:

152070

Hom.:

6392

Cov.:

AF XY:

0.280

AC XY:

20799

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.170

AC:

7035

AN:

41498

American (AMR)

AF:

0.290

AC:

4436

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1158

AN:

3462

East Asian (EAS)

AF:

0.398

AC:

2052

AN:

5158

South Asian (SAS)

AF:

0.241

AC:

1162

AN:

4824

European-Finnish (FIN)

AF:

0.358

AC:

3776

AN:

10560

Middle Eastern (MID)

AF:

0.224

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.325

AC:

22109

AN:

67978

Other (OTH)

AF:

0.286

AC:

603

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1549

3098

4647

6196

7745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

436

872

1308

1744

2180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.313

Hom.:

32286

Bravo

AF:

0.272

Asia WGS

AF:

0.271

AC:

948

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

9.2

(source)

DANN

Benign

0.85

PhyloP100

0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over