9-128838327-C-G

Variant names:

• chr9-128838327-C-G
• rs1831515367
• NM_004059.5:c.242G>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004059.5(KYAT1):​c.242G>C​(p.Gly81Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: KYAT1 NM_004059.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.36
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.242G>C	p.Gly81Ala	missense	Exon 4 of 13	NP_004050.3
	KYAT1-SPOUT1	NM_001414398.1		c.242G>C	p.Gly81Ala	missense	Exon 4 of 23	NP_001401327.1
	KYAT1	NM_001287390.3		c.524G>C	p.Gly175Ala	missense	Exon 6 of 15	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.242G>C	p.Gly81Ala	missense	Exon 4 of 13	ENSP00000302227.3	Q16773-1
	KYAT1	ENST00000651925.1		c.521G>C	p.Gly174Ala	missense	Exon 6 of 29	ENSP00000498386.1	A0A494C066
	KYAT1	ENST00000462722.5	TSL:1	n.388G>C		non_coding_transcript_exon	Exon 4 of 13

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461880 Hom.: 0 Cov.: 33 AF XY: 0.00000825 AC XY: 6 AN XY: 727244

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1112008

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	0.32	D
MutationAssessor	Benign	1.1	L
PhyloP100		4.4
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.6	D
REVEL	Pathogenic	0.66
Sift	Benign	0.17	T
Sift4G	Benign	0.27	T
Polyphen		1.0	D
Vest4		0.39
MutPred		0.50		Loss of helix (P = 0.1706)
MVP		0.93
MPC		0.44
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.62
gMVP		0.75
Mutation Taster		=82/18	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: rs1831515367; hg19: chr9-131600606;