Variant 9-128835400-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004059.5(KYAT1):c.1045A>G(p.Arg349Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000805 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000079 ( 0 hom. )

Consequence

KYAT1
NM_004059.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.61

Variant links:

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 links:

KYAT1-SPOUT1 (HGNC:):

KYAT1-SPOUT1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.058805645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYAT1	NM_004059.5 linkuse as main transcript	c.1045A>G	p.Arg349Gly	missense_variant, splice_region_variant	11/13	ENST00000302586.8	NP_004050.3
KYAT1-SPOUT1	NR_182311.1 linkuse as main transcript	n.1105A>G		splice_region_variant, non_coding_transcript_exon_variant	11/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYAT1	ENST00000302586.8 linkuse as main transcript	c.1045A>G	p.Arg349Gly	missense_variant, splice_region_variant	11/13	1	NM_004059.5	ENSP00000302227	P1	Q16773-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000441

AC:

AN:

249446

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135346

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000787

AC:

115

AN:

1461742

Hom.:

Cov.:

AF XY:

0.0000743

AC XY:

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.000329

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000683

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.0000985

AC:

AN:

152278

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.000117

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000237

AC:

ExAC

AF:

0.0000413

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

The c.1045A>G (p.R349G) alteration is located in exon 11 (coding exon 10) of the KYAT1 gene. This alteration results from a A to G substitution at nucleotide position 1045, causing the arginine (R) at amino acid position 349 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.27

.;T;.

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.051

MetaRNN

Benign

0.059

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

-0.29

.;N;.

MutationTaster

Benign

0.79

D;D;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.57

N;N;N

REVEL

Benign

0.16

Sift

Benign

0.41

T;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.070

B;B;B

Vest4

0.19

MVP

0.65

MPC

0.20

ClinPred

0.061

GERP RS

3.1

Varity_R

0.32

gMVP

0.38

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over