rs12729558

Positions:

• chr1-88937277-C-G
• chr1-88937277-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001008661.3(KYAT3):​c.1303-1032G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 151,862 control chromosomes in the GnomAD database, including 17,005 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.47 (17005 hom., cov: 31)
• Consequence: KYAT3 NM_001008661.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.97

Genes affected

KYAT3 (HGNC:33238): (kynurenine aminotransferase 3) This gene encodes an aminotransferase that transaminates kynurenine to form kynurenic acid, which is a metabolite of tryptophan. Multiple alternatively spliced transcript variants that encode different proteins have been described for this gene. This gene shares 5' exon structure with the RNA binding motif protein, X-linked-like 1 locus on chromosome 1, but the coding sequences are non-overlapping. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYAT3	NM_001008661.3	c.1303-1032G>C		intron_variant		ENST00000260508.9	NP_001008661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYAT3	ENST00000260508.9	c.1303-1032G>C		intron_variant		1	NM_001008661.3	ENSP00000260508	A1
KYAT3	ENST00000370491.7	c.1201-1032G>C		intron_variant		2		ENSP00000359522	P4
KYAT3	ENST00000446900.6	n.1465-1032G>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71551 AN: 151746 Hom.: 16964 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.411

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.320

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.496

Gnomad OTH AF: 0.470

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

GnomAD4 genome AF: 0.472 AC: 71645 AN: 151862 Hom.: 17005 Cov.: 31 AF XY: 0.466 AC XY: 34554 AN XY: 74196

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.411

Gnomad4 EAS AF: 0.457

Gnomad4 SAS AF: 0.320

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.496

Gnomad4 OTH AF: 0.472

Alfa AF: 0.354 Hom.: 938

Bravo AF: 0.480

Asia WGS AF: 0.445 AC: 1545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.26
DANN	Benign	0.45

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

Other links and lift over

dbSNP: rs12729558; hg19: chr1-89402960;