rs16858172

chr2-142878935-C-A

Variant summary

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

The NM_003937.3(KYNU):c.-20+1199C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,124 control chromosomes in the GnomAD database, including 1,496 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 0.11 (1496 hom., cov: 33)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160

Genes affected

KYNU (HGNC:6469): (kynureninase) Kynureninase is a pyridoxal-5'-phosphate (pyridoxal-P) dependent enzyme that catalyzes the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids, respectively. Kynureninase is involved in the biosynthesis of NAD cofactors from tryptophan through the kynurenine pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KYNU	NM_003937.3	c.-20+1199C>A		intron_variant		ENST00000264170.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KYNU	ENST00000264170.9	c.-20+1199C>A		intron_variant		1	NM_003937.3	P1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17138 AN: 152006 Hom.: 1488 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0984

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

GnomAD4 genome AF: 0.113 AC: 17171 AN: 152124 Hom.: 1496 Cov.: 33 AF XY: 0.115 AC XY: 8541 AN XY: 74372

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.221

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.0457

Gnomad4 NFE AF: 0.0469

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0665 Hom.: 266

Bravo AF: 0.124

Asia WGS AF: 0.170 AC: 591 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.95
Dann	Benign	0.35

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: rs16858172; hg19: chr2-143636504;