rs374080396

Variant names:

• chr9-128833769-C-T
• rs374080396
• NM_004059.5:c.1180G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004059.5(KYAT1):​c.1180G>A​(p.Asp394Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000103 in 1,614,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: KYAT1 NM_004059.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.33
• Publications: 4 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.020911783).

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.1180G>A	p.Asp394Asn	missense	Exon 12 of 13	NP_004050.3
	KYAT1	NM_001287390.3		c.1462G>A	p.Asp488Asn	missense	Exon 14 of 15	NP_001274319.1	B7Z4W5
	KYAT1	NM_001352994.2		c.1462G>A	p.Asp488Asn	missense	Exon 14 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.1180G>A	p.Asp394Asn	missense	Exon 12 of 13	ENSP00000302227.3	Q16773-1
	KYAT1	ENST00000651925.1		c.1459G>A	p.Asp487Asn	missense	Exon 14 of 29	ENSP00000498386.1	A0A494C066
	KYAT1	ENST00000462722.5	TSL:1	n.1358G>A		non_coding_transcript_exon	Exon 12 of 13

Frequencies

GnomAD3 genomes AF: 0.000657 AC: 100 AN: 152248 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00239

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 249464 AF XY: 0.000111

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000451 AC: 66 AN: 1461876 Hom.: 0 Cov.: 31 AF XY: 0.0000289 AC XY: 21 AN XY: 727240

African (AFR) AF: 0.00161 AC: 54 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112002

Other (OTH) AF: 0.0000994 AC: 6 AN: 60392

GnomAD4 genome AF: 0.000656 AC: 100 AN: 152366 Hom.: 0 Cov.: 32 AF XY: 0.000671 AC XY: 50 AN XY: 74516

African (AFR) AF: 0.00238 AC: 99 AN: 41590

American (AMR) AF: 0.0000653 AC: 1 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000367 Hom.: 0

Bravo AF: 0.000699

ESP6500AA AF: 0.00100 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000116 AC: 14

Asia WGS AF: 0.000577 AC: 2 AN: 3478

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	Benign	-0.37	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D
Eigen	Benign	-0.036
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.021	T
MetaSVM	Uncertain	0.29	D
MutationAssessor	Benign	1.3	L
PhyloP100		3.3
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.30
Sift	Benign	0.16	T
Sift4G	Benign	0.20	T
Polyphen		0.64	P
Vest4		0.26
MVP		0.77
MPC		0.17
ClinPred		0.052	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.40
gMVP		0.81
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.20		Position offset: -29

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs374080396; hg19: chr9-131596048;