Variant 9-128847452-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001287390.3(KYAT1):c.77C>T(p.Thr26Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00885 in 1,535,734 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 24 hom., cov: 32)

Exomes 𝑓: 0.0089 ( 127 hom. )

Consequence

KYAT1
NM_001287390.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.720

Variant links:

Genes affected

ENSG00000286112 (HGNC:):

ENSG00000286112 links:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014366806).

BP6

Variant 9-128847452-G-A is Benign according to our data. Variant chr9-128847452-G-A is described in ClinVar as [Benign]. Clinvar id is 782286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00847 (1290/152316) while in subpopulation AMR AF= 0.0385 (589/15304). AF 95% confidence interval is 0.0359. There are 24 homozygotes in gnomad4. There are 649 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYAT1	NM_004059.5 linkuse as main transcript	c.-6-2041C>T		intron_variant		ENST00000302586.8	NP_004050.3	Q16773-1A8K563

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000286112	ENST00000651925.1 linkuse as main transcript	c.77C>T	p.Thr26Ile	missense_variant	2/29			ENSP00000498386.1		A0A494C066
KYAT1	ENST00000302586.8 linkuse as main transcript	c.-6-2041C>T		intron_variant		1	NM_004059.5	ENSP00000302227.3		Q16773-1

Frequencies

GnomAD3 genomes

AF:

0.00838

AC:

1276

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00220

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0376

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00518

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00763

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.0133

AC:

1791

AN:

134356

Hom.:

AF XY:

0.0116

AC XY:

848

AN XY:

73166

show subpopulations

Gnomad AFR exome

AF:

0.00233

Gnomad AMR exome

AF:

0.0473

Gnomad ASJ exome

AF:

0.000604

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00561

Gnomad FIN exome

AF:

0.00186

Gnomad NFE exome

AF:

0.00808

Gnomad OTH exome

AF:

0.0131

GnomAD4 exome

AF:

0.00889

AC:

12295

AN:

1383418

Hom.:

127

Cov.:

AF XY:

0.00860

AC XY:

5870

AN XY:

682676

show subpopulations

Gnomad4 AFR exome

AF:

0.00142

Gnomad4 AMR exome

AF:

0.0516

Gnomad4 ASJ exome

AF:

0.000556

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00550

Gnomad4 FIN exome

AF:

0.00233

Gnomad4 NFE exome

AF:

0.00870

Gnomad4 OTH exome

AF:

0.00832

GnomAD4 genome

AF:

0.00847

AC:

1290

AN:

152316

Hom.:

Cov.:

AF XY:

0.00871

AC XY:

649

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00219

Gnomad4 AMR

AF:

0.0385

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00518

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00763

Gnomad4 OTH

AF:

0.0166

Alfa

AF:

0.00255

Hom.:

Bravo

AF:

0.0112

TwinsUK

AF:

0.00674

AC:

ALSPAC

AF:

0.00727

AC:

ExAC

AF:

0.00481

AC:

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.42

CADD

Benign

4.6

DANN

Benign

0.90

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.85

PROVEAN

Benign

-0.32

REVEL

Benign

0.11

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0070

Polyphen

0.047

Vest4

0.23

ClinPred

0.0068

GERP RS

0.086

gMVP

0.13

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