rs10496940

Positions:

• chr2-143025128-C-A
• chr2-143025128-C-T

Variant summary

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

The NM_003937.3(KYNU):​c.903-4499C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,946 control chromosomes in the GnomAD database, including 1,097 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 0.12 (1097 hom., cov: 32)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYNU	NM_003937.3	c.903-4499C>A		intron_variant		ENST00000264170.9	NP_003928.1
KYNU	NM_001199241.2	c.903-4499C>A		intron_variant			NP_001186170.1
KYNU	XM_047446250.1	c.903-4499C>A		intron_variant			XP_047302206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000264170.9	c.903-4499C>A		intron_variant		1	NM_003937.3	ENSP00000264170	P1
KYNU	ENST00000409512.5	c.903-4499C>A		intron_variant		1		ENSP00000386731	P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17553 AN: 151828 Hom.: 1096 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0667

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.116 AC: 17578 AN: 151946 Hom.: 1097 Cov.: 32 AF XY: 0.114 AC XY: 8480 AN XY: 74304

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0667

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0740

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0487 Hom.: 47

Bravo AF: 0.116

Asia WGS AF: 0.180 AC: 624 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.50
DANN	Benign	0.61

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: rs10496940; hg19: chr2-143782697;