NM_004059.5:c.439-19A>G

Variant names:

• chr9-128837832-T-C
• rs2280841
• NM_004059.5:c.439-19A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004059.5(KYAT1):​c.439-19A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.724 in 1,612,462 control chromosomes in the GnomAD database, including 429,631 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 0.64 (33704 hom., cov: 31)
  • Exomes 𝑓: 0.73 (395927 hom.)
• Consequence: KYAT1 NM_004059.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486

Genes affected

KYAT1 (HGNC:1564): (kynurenine aminotransferase 1) This gene encodes a cytosolic enzyme that is responsible for the metabolism of cysteine conjugates of certain halogenated alkenes and alkanes. This metabolism can form reactive metabolites leading to nephrotoxicity and neurotoxicity. Increased levels of this enzyme have been linked to schizophrenia. Multiple transcript variants that encode different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ENSG00000286112 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KYAT1	NM_004059.5	c.439-19A>G		intron_variant	Intron 5 of 12	ENST00000302586.8	NP_004050.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KYAT1	ENST00000302586.8	c.439-19A>G		intron_variant	Intron 5 of 12	1	NM_004059.5	ENSP00000302227.3
ENSG00000286112	ENST00000651925.1	c.718-19A>G		intron_variant	Intron 7 of 28			ENSP00000498386.1

Frequencies

GnomAD3 genomes AF: 0.640 AC: 97159 AN: 151894 Hom.: 33697 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.724

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.661

GnomAD3 exomes AF: 0.720 AC: 179109 AN: 248868 Hom.: 66143 AF XY: 0.719 AC XY: 97040 AN XY: 135050

Gnomad AFR exome AF: 0.336

Gnomad AMR exome AF: 0.801

Gnomad ASJ exome AF: 0.757

Gnomad EAS exome AF: 0.727

Gnomad SAS exome AF: 0.623

Gnomad FIN exome AF: 0.829

Gnomad NFE exome AF: 0.748

Gnomad OTH exome AF: 0.731

GnomAD4 exome AF: 0.733 AC: 1069991 AN: 1460450 Hom.: 395927 Cov.: 42 AF XY: 0.731 AC XY: 531029 AN XY: 726586

Gnomad4 AFR exome AF: 0.331

Gnomad4 AMR exome AF: 0.796

Gnomad4 ASJ exome AF: 0.763

Gnomad4 EAS exome AF: 0.752

Gnomad4 SAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.831

Gnomad4 NFE exome AF: 0.746

Gnomad4 OTH exome AF: 0.707

GnomAD4 genome AF: 0.639 AC: 97203 AN: 152012 Hom.: 33704 Cov.: 31 AF XY: 0.645 AC XY: 47897 AN XY: 74288

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.756

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.724

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.749

Gnomad4 OTH AF: 0.661

Alfa AF: 0.689 Hom.: 8638

Bravo AF: 0.624

Asia WGS AF: 0.656 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.54
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2280841; hg19: chr9-131600111;