2-142990390-C-T

Variant names:

• chr2-142990390-C-T
• rs10496938
• NM_003937.3:c.902+4369C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

KYNU Gene-Disease associations (from GenCC):

• vertebral, cardiac, renal, and limb defects syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• encephalopathy due to hydroxykynureninuria

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• congenital vertebral-cardiac-renal anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 134 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KYNU	NM_003937.3	c.902+4369C>T		intron_variant	Intron 10 of 13	ENST00000264170.9	NP_003928.1
KYNU	NM_001199241.2	c.902+4369C>T		intron_variant	Intron 11 of 14		NP_001186170.1
KYNU	XM_047446250.1	c.902+4369C>T		intron_variant	Intron 10 of 12		XP_047302206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000264170.9	c.902+4369C>T		intron_variant	Intron 10 of 13	1	NM_003937.3	ENSP00000264170.4
KYNU	ENST00000409512.5	c.902+4369C>T		intron_variant	Intron 11 of 14	1		ENSP00000386731.1

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

African (AFR) AF: 0.00836 AC: 347 AN: 41500

American (AMR) AF: 0.0246 AC: 374 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0222 AC: 77 AN: 3468

East Asian (EAS) AF: 0.0218 AC: 112 AN: 5140

South Asian (SAS) AF: 0.0482 AC: 232 AN: 4818

European-Finnish (FIN) AF: 0.0760 AC: 804 AN: 10578

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0511 AC: 3470 AN: 67848

Other (OTH) AF: 0.0346 AC: 73 AN: 2110

Alfa AF: 0.0439 Hom.: 101

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
PhyloP100		-0.28
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10496938; hg19: chr2-143747959;