2-142904998-T-C

Position:

• chr2-142904998-T-C

Variant summary

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

The NM_003937.3(KYNU):​c.170-13611T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,990 control chromosomes in the GnomAD database, including 24,839 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 0.56 (24839 hom., cov: 32)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.17

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYNU	NM_003937.3	c.170-13611T>C		intron_variant		ENST00000264170.9	NP_003928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000264170.9	c.170-13611T>C		intron_variant		1	NM_003937.3	ENSP00000264170.4

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84954 AN: 151872 Hom.: 24797 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.560 AC: 85044 AN: 151990 Hom.: 24839 Cov.: 32 AF XY: 0.567 AC XY: 42127 AN XY: 74298

Gnomad4 AFR AF: 0.710

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.690

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.527

Alfa AF: 0.502 Hom.: 2392

Bravo AF: 0.574

Asia WGS AF: 0.670 AC: 2327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.90
DANN	Benign	0.21

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: rs6429992; hg19: chr2-143662567;