9-128835398-CCT-ACC

Variant names:

• chr9-128835398-CCT-ACC
• NM_004059.5:c.1045_1047delAGGinsGGT
• KYAT1 p.Arg349Gly

Variant summary

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

The NM_004059.5(KYAT1):​c.1045_1047delAGGinsGGT​(p.Arg349Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: KYAT1 NM_004059.5 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.61
• Publications: 0 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 0 ACMG points.

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.1045_1047delAGGinsGGT	p.Arg349Gly	missense splice_region	N/A	NP_004050.3
	KYAT1-SPOUT1	NM_001414398.1		c.1045_1047delAGGinsGGT	p.Arg349Gly	missense splice_region	N/A	NP_001401327.1
	KYAT1	NM_001287390.3		c.1327_1329delAGGinsGGT	p.Arg443Gly	missense splice_region	N/A	NP_001274319.1	B7Z4W5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYAT1	ENST00000302586.8	TSL:1 MANE Select	c.1045_1047delAGGinsGGT	p.Arg349Gly	missense splice_region	N/A	ENSP00000302227.3	Q16773-1
	KYAT1	ENST00000651925.1		c.1324_1326delAGGinsGGT	p.Arg442Gly	missense splice_region	N/A	ENSP00000498386.1	A0A494C066
	KYAT1	ENST00000462722.5	TSL:1	n.1223_1225delAGGinsGGT		splice_region non_coding_transcript_exon	Exon 11 of 13

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6

Splicing

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

hg19: chr9-131597677;