2-143040620-A-G

Position:

• chr2-143040620-A-G

Variant summary

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

The ENST00000264170.9(KYNU):​c.1234A>G​(p.Lys412Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 1,606,390 control chromosomes in the GnomAD database, including 24,512 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.16 (1959 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22553 hom.)
• Consequence: KYNU ENST00000264170.9 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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 (MetaRNN=0.0051650703).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYNU	NM_003937.3	c.1234A>G	p.Lys412Glu	missense_variant	13/14	ENST00000264170.9	NP_003928.1
KYNU	NM_001199241.2	c.1234A>G	p.Lys412Glu	missense_variant	14/15		NP_001186170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000264170.9	c.1234A>G	p.Lys412Glu	missense_variant	13/14	1	NM_003937.3	ENSP00000264170	P1
KYNU	ENST00000409512.5	c.1234A>G	p.Lys412Glu	missense_variant	14/15	1		ENSP00000386731	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23861 AN: 151946 Hom.: 1954 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0887

Gnomad EAS AF: 0.268

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.152

GnomAD3 exomes AF: 0.160 AC: 39410 AN: 246126 Hom.: 3406 AF XY: 0.161 AC XY: 21445 AN XY: 132910

Gnomad AFR exome AF: 0.134

Gnomad AMR exome AF: 0.0982

Gnomad ASJ exome AF: 0.0895

Gnomad EAS exome AF: 0.279

Gnomad SAS exome AF: 0.173

Gnomad FIN exome AF: 0.155

Gnomad NFE exome AF: 0.167

Gnomad OTH exome AF: 0.154

GnomAD4 exome AF: 0.172 AC: 250241 AN: 1454326 Hom.: 22553 Cov.: 31 AF XY: 0.172 AC XY: 124012 AN XY: 722906

Gnomad4 AFR exome AF: 0.128

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.0908

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.173

Gnomad4 FIN exome AF: 0.154

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.157 AC: 23901 AN: 152064 Hom.: 1959 Cov.: 32 AF XY: 0.157 AC XY: 11643 AN XY: 74356

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0887

Gnomad4 EAS AF: 0.269

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.154

Alfa AF: 0.167 Hom.: 4069

Bravo AF: 0.152

TwinsUK AF: 0.174 AC: 647

ALSPAC AF: 0.179 AC: 690

ESP6500AA AF: 0.139 AC: 614

ESP6500EA AF: 0.172 AC: 1481

ExAC AF: 0.162 AC: 19625

Asia WGS AF: 0.209 AC: 726 AN: 3478

EpiCase AF: 0.169

EpiControl AF: 0.160

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.65	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	13
DANN	Benign	0.23
DEOGEN2	Benign	0.037	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.56	.;T
MetaRNN	Benign	0.0052	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.098
Sift	Benign	0.69	T;T
Sift4G	Benign	0.52	T;T
Polyphen		0.0	B;B
Vest4		0.17
MPC		0.044
ClinPred		0.0045	T
GERP RS		4.4
Varity_R		0.18
gMVP		0.54

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: rs9013; hg19: chr2-143798189; COSMIC: COSV51580314;