1-241566754-C-T

Position:

• chr1-241566754-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

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/exons	MANE	UniProt
KMO	NM_003679.5	c.809+142C>T		intron_variant		ENST00000366559.9
KMO	NM_001410944.1	c.809+142C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KMO	ENST00000366559.9	c.809+142C>T		intron_variant		1	NM_003679.5	P2
KMO	ENST00000366558.7	c.809+142C>T		intron_variant		1		A2
KMO	ENST00000366557.8	c.809+142C>T		intron_variant		5
KMO	ENST00000431245.2	n.398+142C>T		intron_variant, non_coding_transcript_variant		3

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

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.: 32 AF XY: 0.280 AC XY: 20799 AN XY: 74320

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

Other links and lift over

dbSNP: rs2275163; hg19: chr1-241730054; COSMIC: COSV63806284; COSMIC: COSV63806284;