chr2-142878935-C-A

Variant names:

• chr2-142878935-C-A
• rs16858172
• NM_003937.3:c.-20+1199C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003937.3(KYNU):​c.-20+1199C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,124 control chromosomes in the GnomAD database, including 1,496 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 0.11 (1496 hom., cov: 33)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 3 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).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003937.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYNU	NM_003937.3	MANE Select	c.-20+1199C>A		intron	N/A	NP_003928.1
	KYNU	NM_001199241.2		c.-106+1199C>A		intron	N/A	NP_001186170.1
	KYNU	NM_001032998.2		c.-20+1199C>A		intron	N/A	NP_001028170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYNU	ENST00000264170.9	TSL:1 MANE Select	c.-20+1199C>A		intron	N/A	ENSP00000264170.4
	KYNU	ENST00000409512.5	TSL:1	c.-106+1199C>A		intron	N/A	ENSP00000386731.1
	KYNU	ENST00000375773.6	TSL:1	c.-20+1199C>A		intron	N/A	ENSP00000364928.2

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17138 AN: 152006 Hom.: 1488 Cov.: 33

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.222

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.0457

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0984

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

GnomAD4 genome AF: 0.113 AC: 17171 AN: 152124 Hom.: 1496 Cov.: 33 AF XY: 0.115 AC XY: 8541 AN XY: 74372

African (AFR) AF: 0.234 AC: 9695 AN: 41476

American (AMR) AF: 0.103 AC: 1568 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1146 AN: 5184

South Asian (SAS) AF: 0.122 AC: 589 AN: 4820

European-Finnish (FIN) AF: 0.0457 AC: 483 AN: 10578

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0469 AC: 3188 AN: 67994

Other (OTH) AF: 0.101 AC: 213 AN: 2116

Alfa AF: 0.0654 Hom.: 282

Bravo AF: 0.124

Asia WGS AF: 0.170 AC: 591 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.95
DANN	Benign	0.35
PhyloP100		0.16
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: rs16858172; hg19: chr2-143636504;