Genetic Variant KMO:c.957+9T>A (chr1-241568656-T-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_ModerateBP6_Very_StrongBS2

The NM_003679.5(KMO):c.957+9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00262 in 1,610,304 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0024 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0027 ( 8 hom. )

Consequence

KMO
NM_003679.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.526

Publications

0 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 1-241568656-T-A is Benign according to our data. Variant chr1-241568656-T-A is described in ClinVar as Benign. ClinVar VariationId is 773477.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003679.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMO	NM_003679.5	MANE Select	c.957+9T>A		intron	N/A	NP_003670.2	O15229-1
	KMO	NM_001410944.1		c.957+9T>A		intron	N/A	NP_001397873.1	O15229-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
KMO	ENST00000366559.9	TSL:1 MANE Select	c.957+9T>A	intron	N/A	ENSP00000355517.4	O15229-1
KMO	ENST00000366558.7	TSL:1	c.957+9T>A	intron	N/A	ENSP00000355516.3	O15229-2
KMO	ENST00000881617.1		c.957+9T>A	intron	N/A	ENSP00000551676.1

Frequencies

GnomAD3 genomes

AF:

0.00236

AC:

359

AN:

151858

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000607

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00256

Gnomad ASJ

AF:

0.0136

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00249

AC:

616

AN:

247382

AF XY:

0.00265

show subpopulations

Gnomad AFR exome

AF:

0.000248

Gnomad AMR exome

AF:

0.00230

Gnomad ASJ exome

AF:

0.00874

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000652

Gnomad NFE exome

AF:

0.00335

Gnomad OTH exome

AF:

0.00333

GnomAD4 exome

AF:

0.00265

AC:

3866

AN:

1458328

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

1993

AN XY:

725328

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

33156

American (AMR)

AF:

0.00214

AC:

AN:

44348

Ashkenazi Jewish (ASJ)

AF:

0.00975

AC:

254

AN:

26054

East Asian (EAS)

AF:

0.00

AC:

AN:

39510

South Asian (SAS)

AF:

0.00152

AC:

131

AN:

86018

European-Finnish (FIN)

AF:

0.000732

AC:

AN:

53300

Middle Eastern (MID)

AF:

0.00435

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00282

AC:

3131

AN:

1110020

Other (OTH)

AF:

0.00304

AC:

183

AN:

60172

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

186

371

557

742

928

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<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:

0.00236

AC:

359

AN:

151976

Hom.:

Cov.:

AF XY:

0.00225

AC XY:

167

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.000606

AC:

AN:

41278

American (AMR)

AF:

0.00255

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.0136

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00248

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000660

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00319

AC:

217

AN:

68022

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00351

Hom.:

Bravo

AF:

0.00253

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.79

PhyloP100

0.53

PromoterAI

-0.0016

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over