9-128837832-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001414398.1(KYAT1-SPOUT1):​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-SPOUT1 NM_001414398.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.486
• Publications: 12 publications found

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]

KYAT1 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001414398.1. 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
	KYAT1	NM_004059.5	MANE Select	c.439-19A>G		intron	N/A	NP_004050.3
	KYAT1-SPOUT1	NM_001414398.1		c.439-19A>G		intron	N/A	NP_001401327.1
	KYAT1	NM_001287390.3		c.721-19A>G		intron	N/A	NP_001274319.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYAT1	ENST00000302586.8	TSL:1 MANE Select	c.439-19A>G		intron	N/A	ENSP00000302227.3
	KYAT1	ENST00000651925.1		c.718-19A>G		intron	N/A	ENSP00000498386.1
	KYAT1	ENST00000462722.5	TSL:1	n.585-19A>G		intron	N/A

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

GnomAD2 exomes AF: 0.720 AC: 179109 AN: 248868 AF XY: 0.719

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 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

African (AFR) AF: 0.331 AC: 11072 AN: 33454

American (AMR) AF: 0.796 AC: 35598 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 19911 AN: 26110

East Asian (EAS) AF: 0.752 AC: 29838 AN: 39684

South Asian (SAS) AF: 0.625 AC: 53896 AN: 86218

European-Finnish (FIN) AF: 0.831 AC: 44324 AN: 53332

Middle Eastern (MID) AF: 0.695 AC: 4003 AN: 5758

European-Non Finnish (NFE) AF: 0.746 AC: 828658 AN: 1110846

Other (OTH) AF: 0.707 AC: 42691 AN: 60342

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

African (AFR) AF: 0.346 AC: 14362 AN: 41456

American (AMR) AF: 0.756 AC: 11536 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.768 AC: 2664 AN: 3468

East Asian (EAS) AF: 0.724 AC: 3730 AN: 5152

South Asian (SAS) AF: 0.615 AC: 2959 AN: 4812

European-Finnish (FIN) AF: 0.828 AC: 8762 AN: 10584

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50886 AN: 67960

Other (OTH) AF: 0.661 AC: 1396 AN: 2112

Alfa AF: 0.681 Hom.: 8689

Bravo AF: 0.624

Asia WGS AF: 0.656 AC: 2283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.54
DANN	Benign	0.46
PhyloP100		-0.49
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

Other links and lift over

dbSNP: rs2280841; hg19: chr9-131600111;