2-142889750-T-C

Variant names:

• chr2-142889750-T-C
• rs1438266
• NM_003937.3:c.169+4214T>C

Variant summary

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

The NM_003937.3(KYNU):​c.169+4214T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,008 control chromosomes in the GnomAD database, including 24,231 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 0.55 (24231 hom., cov: 32)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0140
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 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.169+4214T>C		intron	N/A	NP_003928.1	Q16719-1
	KYNU	NM_001199241.2		c.169+4214T>C		intron	N/A	NP_001186170.1	Q16719-1
	KYNU	NM_001032998.2		c.169+4214T>C		intron	N/A	NP_001028170.1	Q16719-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYNU	ENST00000264170.9	TSL:1 MANE Select	c.169+4214T>C		intron	N/A	ENSP00000264170.4	Q16719-1
	KYNU	ENST00000409512.5	TSL:1	c.169+4214T>C		intron	N/A	ENSP00000386731.1	Q16719-1
	KYNU	ENST00000375773.6	TSL:1	c.169+4214T>C		intron	N/A	ENSP00000364928.2	Q16719-2

Frequencies

GnomAD3 genomes AF: 0.552 AC: 83859 AN: 151890 Hom.: 24185 Cov.: 32

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.620

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.552 AC: 83954 AN: 152008 Hom.: 24231 Cov.: 32 AF XY: 0.560 AC XY: 41621 AN XY: 74306

African (AFR) AF: 0.701 AC: 29081 AN: 41456

American (AMR) AF: 0.620 AC: 9479 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1468 AN: 3470

East Asian (EAS) AF: 0.590 AC: 3044 AN: 5162

South Asian (SAS) AF: 0.685 AC: 3299 AN: 4814

European-Finnish (FIN) AF: 0.524 AC: 5527 AN: 10554

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30381 AN: 67960

Other (OTH) AF: 0.513 AC: 1081 AN: 2106

Alfa AF: 0.548 Hom.: 4334

Bravo AF: 0.566

Asia WGS AF: 0.667 AC: 2318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.54
PhyloP100		-0.014
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: rs1438266; hg19: chr2-143647319;