Genetic Variant NM_003679.5: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

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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