rs17853193

Variant names:

• chr9-128833585-T-C
• rs17853193
• NM_004059.5:c.1268A>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_004059.5(KYAT1):​c.1268A>G​(p.Ter423Trpext*?) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: KYAT1 NM_004059.5 stop_lost
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849
• Publications: 1 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_004059.5 Downstream stopcodon found after 442 codons.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004059.5. 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
	KYAT1	NM_004059.5	MANE Select	c.1268A>G	p.Ter423Trpext*?	stop_lost	Exon 13 of 13	NP_004050.3
	KYAT1	NM_001287390.3		c.1550A>G	p.Ter517Trpext*?	stop_lost	Exon 15 of 15	NP_001274319.1	B7Z4W5
	KYAT1	NM_001352994.2		c.1550A>G	p.Ter517Trpext*?	stop_lost	Exon 15 of 15	NP_001339923.1	B7Z4W5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYAT1	ENST00000302586.8	TSL:1 MANE Select	c.1268A>G	p.Ter423Trpext*?	stop_lost	Exon 13 of 13	ENSP00000302227.3	Q16773-1
	KYAT1	ENST00000651925.1		c.1547A>G	p.Ter516Trpext*?	stop_lost	Exon 15 of 29	ENSP00000498386.1	A0A494C066
	KYAT1	ENST00000462722.5	TSL:1	n.1446A>G		non_coding_transcript_exon	Exon 13 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	2.5
DANN	Benign	0.48
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.021	N
PhyloP100		-0.85
Vest4		0.020
GERP RS		-7.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=153/47	polymorphism

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: rs17853193; hg19: chr9-131595864;