2-142990390-C-T

Position:

• chr2-142990390-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_003937.3(KYNU):​c.902+4369C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 151,896 control chromosomes in the GnomAD database, including 134 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 0.036 (134 hom., cov: 32)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0363 (5517/151896) while in subpopulation NFE AF= 0.0511 (3470/67848). AF 95% confidence interval is 0.0497. There are 134 homozygotes in gnomad4. There are 2769 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 134 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KYNU	NM_003937.3	c.902+4369C>T		intron_variant		ENST00000264170.9
KYNU	NM_001199241.2	c.902+4369C>T		intron_variant
KYNU	XM_047446250.1	c.902+4369C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KYNU	ENST00000264170.9	c.902+4369C>T		intron_variant		1	NM_003937.3	P1
KYNU	ENST00000409512.5	c.902+4369C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0363 AC: 5517 AN: 151778 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.00839

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0247

Gnomad ASJ AF: 0.0222

Gnomad EAS AF: 0.0215

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0760

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0511

Gnomad OTH AF: 0.0350

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

GnomAD4 genome AF: 0.0363 AC: 5517 AN: 151896 Hom.: 134 Cov.: 32 AF XY: 0.0373 AC XY: 2769 AN XY: 74226

Gnomad4 AFR AF: 0.00836

Gnomad4 AMR AF: 0.0246

Gnomad4 ASJ AF: 0.0222

Gnomad4 EAS AF: 0.0218

Gnomad4 SAS AF: 0.0482

Gnomad4 FIN AF: 0.0760

Gnomad4 NFE AF: 0.0511

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.0440 Hom.: 94

Bravo AF: 0.0299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.66
DANN	Benign	0.57

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: rs10496938; hg19: chr2-143747959;