1-241566754-C-T

Variant names:

• chr1-241566754-C-T
• rs2275163
• NM_003679.5:c.809+142C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 23 publications found

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

ACMG classification

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.

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.809+142C>T		intron	N/A	NP_003670.2	O15229-1
	KMO	NM_001410944.1		c.809+142C>T		intron	N/A	NP_001397873.1	O15229-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KMO	ENST00000366559.9	TSL:1 MANE Select	c.809+142C>T		intron	N/A	ENSP00000355517.4	O15229-1
	KMO	ENST00000366558.7	TSL:1	c.809+142C>T		intron	N/A	ENSP00000355516.3	O15229-2
	KMO	ENST00000881617.1		c.809+142C>T		intron	N/A	ENSP00000551676.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42529 AN: 151952 Hom.: 6384 Cov.: 32

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

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

GnomAD4 genome AF: 0.280 AC: 42557 AN: 152070 Hom.: 6392 Cov.: 32 AF XY: 0.280 AC XY: 20799 AN XY: 74320

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: 66 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22109 AN: 67978

Other (OTH) AF: 0.286 AC: 603 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	9.2
DANN	Benign	0.85
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2275163;

hg19: chr1-241730054;

COSMIC: COSV63806284;

COSMIC: COSV63806284;