2-143033445-G-T

Position:

• chr2-143033445-G-T

Variant summary

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

The NM_003937.3(KYNU):​c.1041+124G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 810,176 control chromosomes in the GnomAD database, including 6,731 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 (1127 hom., cov: 32)
  • Exomes 𝑓: 0.12 (5604 hom.)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYNU	NM_003937.3	c.1041+124G>T		intron_variant		ENST00000264170.9	NP_003928.1
KYNU	NM_001199241.2	c.1041+124G>T		intron_variant			NP_001186170.1
KYNU	XM_047446250.1	c.1041+124G>T		intron_variant			XP_047302206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000264170.9	c.1041+124G>T		intron_variant		1	NM_003937.3	ENSP00000264170	P1
KYNU	ENST00000409512.5	c.1041+124G>T		intron_variant		1		ENSP00000386731	P1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17839 AN: 152084 Hom.: 1125 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0663

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0733

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.115

GnomAD4 exome AF: 0.122 AC: 80001 AN: 657974 Hom.: 5604 AF XY: 0.122 AC XY: 43537 AN XY: 355966

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.0814

Gnomad4 ASJ exome AF: 0.0650

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.127

Gnomad4 FIN exome AF: 0.0797

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.117 AC: 17865 AN: 152202 Hom.: 1127 Cov.: 32 AF XY: 0.116 AC XY: 8613 AN XY: 74416

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.0663

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0733

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.117

Alfa AF: 0.112 Hom.: 1386

Bravo AF: 0.118

Asia WGS AF: 0.182 AC: 634 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.43
DANN	Benign	0.49

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: rs2304700; hg19: chr2-143791014; COSMIC: COSV51583020;