rs10496940

Variant names:

• chr2-143025128-C-A
• rs10496940
• NM_003937.3:c.903-4499C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-143025128-C-A
• chr2-143025128-C-T

Variant summary

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

The NM_003937.3(KYNU):​c.903-4499C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 151,946 control chromosomes in the GnomAD database, including 1,097 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 (1097 hom., cov: 32)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.238 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYNU	NM_003937.3	MANE Select	c.903-4499C>A		intron	N/A	NP_003928.1	Q16719-1
	KYNU	NM_001199241.2		c.903-4499C>A		intron	N/A	NP_001186170.1	Q16719-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYNU	ENST00000264170.9	TSL:1 MANE Select	c.903-4499C>A		intron	N/A	ENSP00000264170.4	Q16719-1
	KYNU	ENST00000409512.5	TSL:1	c.903-4499C>A		intron	N/A	ENSP00000386731.1	Q16719-1
	KYNU	ENST00000852084.1		c.1029-4499C>A		intron	N/A	ENSP00000522143.1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17553 AN: 151828 Hom.: 1096 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0667

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0740

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.113

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

GnomAD4 genome AF: 0.116 AC: 17578 AN: 151946 Hom.: 1097 Cov.: 32 AF XY: 0.114 AC XY: 8480 AN XY: 74304

African (AFR) AF: 0.105 AC: 4357 AN: 41432

American (AMR) AF: 0.103 AC: 1570 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0667 AC: 231 AN: 3462

East Asian (EAS) AF: 0.249 AC: 1290 AN: 5172

South Asian (SAS) AF: 0.134 AC: 645 AN: 4820

European-Finnish (FIN) AF: 0.0740 AC: 779 AN: 10534

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8354 AN: 67944

Other (OTH) AF: 0.115 AC: 242 AN: 2108

Alfa AF: 0.0512 Hom.: 50

Bravo AF: 0.116

Asia WGS AF: 0.180 AC: 624 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.50
DANN	Benign	0.61
PhyloP100		-1.1
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: rs10496940; hg19: chr2-143782697;