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

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

Gnomad4 AFR exome

AF:

0.164

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.392

Gnomad4 SAS exome

AF:

0.257

Gnomad4 FIN exome

AF:

0.353

Gnomad4 NFE exome

AF:

0.320

Gnomad4 OTH exome

AF:

0.314

GnomAD4 genome

AF:

0.280

AC:

42557

AN:

152070

Hom.:

6392

Cov.:

AF XY:

0.280

AC XY:

20799

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.334

Gnomad4 EAS

AF:

0.398

Gnomad4 SAS

AF:

0.241

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.325

Gnomad4 OTH

AF:

0.286

Alfa

AF:

0.318

Hom.:

16169

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

DANN

Benign

0.85

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

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over