rs10496935

chr2-142988925-C-Gchr2-142988925-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.902+2904C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,558,488 control chromosomes in the GnomAD database, including 42,147 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 0.26 (5799 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36348 hom.)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KYNU	NM_003937.3	c.902+2904C>G		intron_variant		ENST00000264170.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KYNU	ENST00000264170.9	c.902+2904C>G		intron_variant		1	NM_003937.3	P1
KYNU	ENST00000375773.6	c.*38+21C>G		intron_variant		1
KYNU	ENST00000409512.5	c.902+2904C>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39670 AN: 151616 Hom.: 5787 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.217 AC: 305547 AN: 1406754 Hom.: 36348 Cov.: 24 AF XY: 0.221 AC XY: 155111 AN XY: 702846

Gnomad4 AFR exome AF: 0.373

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.161

Gnomad4 EAS exome AF: 0.476

Gnomad4 SAS exome AF: 0.318

Gnomad4 FIN exome AF: 0.215

Gnomad4 NFE exome AF: 0.196

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.262 AC: 39713 AN: 151734 Hom.: 5799 Cov.: 32 AF XY: 0.264 AC XY: 19611 AN XY: 74156

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.205

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.473

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.199

Gnomad4 OTH AF: 0.239

Alfa AF: 0.129 Hom.: 213

Bravo AF: 0.264

Asia WGS AF: 0.375 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.46

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: rs10496935; hg19: chr2-143746494; COSMIC: COSV51594113;