2-142881000-T-G

Position:

• chr2-142881000-T-G

Variant summary

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

The NM_003937.3(KYNU):​c.-20+3264T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.159 in 152,248 control chromosomes in the GnomAD database, including 3,096 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 0.16 (3096 hom., cov: 32)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYNU	NM_003937.3	c.-20+3264T>G		intron_variant		ENST00000264170.9	NP_003928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000264170.9	c.-20+3264T>G		intron_variant		1	NM_003937.3	ENSP00000264170	P1

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24214 AN: 152130 Hom.: 3084 Cov.: 32

Gnomad AFR AF: 0.332

Gnomad AMI AF: 0.0604

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.0787

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0552

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.159 AC: 24261 AN: 152248 Hom.: 3096 Cov.: 32 AF XY: 0.161 AC XY: 12003 AN XY: 74440

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.0787

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.0526

Gnomad4 NFE AF: 0.0552

Gnomad4 OTH AF: 0.153

Alfa AF: 0.0911 Hom.: 1165

Bravo AF: 0.185

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.79
DANN	Benign	0.60

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: rs1439875; hg19: chr2-143638569;