Variant chr2-142954375-CTTTTATAAAAGGTGTATTTTAATTTGATGTTAGAAACAACGAACTTTAAAAATGTAATTGGCCTTAATATCTTTTTAGATTCCTTTGAAGATATACTTAGCACAAAAATATGCTCCTTGGGAATTTGACAATTGAGCTGATAATAGGATATATCATTTTTAGTTTACAGGCAAAAGCAAATGCTTCATTATTTTGTTGTTATTTACTACATCATAAAAGAAATTTAATTTTAGCTAGCTGTGTGCATCTAAGTCCAGATATCATTTGATAAAATGAGTCAAGTGGGAAAACTTCCATTTCTTTGTGATGACACATCAAATATGCCCTTATCTCTAAAGACATTAAGAATGATTGAGTGAAGTCTTCCTACTTTGTTTTTTCAGTATCTTTAGACATAGTACAAACATCTAAATTACGATATGTTTATTTTACAGGAGCCAATGAGAAAGAAATAGCCCTAATGAATGCTTTGACTGTAAATTTACATCTTCTAATGGTAAGTTTTCTTTCCCACTAATGTTTAGAACACATTCATTTACAGAATCTGATGTTTTTCTATCTTTAATTCATGAGCTTCTGGGGGTTTACTTATTTAAAAATAAATTGTGAGGTTATTTTCATTTTTACTAGGAAATGCTGGACCATGATATAATAGCTTCTTCCTAATCATGGAAGAGTTGACTCTTGAGAAGAGCTTTAGAATAATGAACAGTTCTTGTCTGGGAAAATAAAGAATAAGAGCCATAATGGGTAAATAGGCAAACTACATGCAAGCCTACAAAACAGTGATGTACAATGCTAGCAAAGCACTGACCTTTTTGGAAAGACAATTTTCTAATGGCTTCAGCAGAGTGAGTTAGTGGA-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5

The NM_003937.3(KYNU):c.374-433_435+369del variant causes a exon loss, splice acceptor, splice donor, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

KYNU
NM_003937.3 exon_loss, splice_acceptor, splice_donor, splice_region, intron

Scores

Not classified

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 2.96

Variant links:

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 links:

KYNU (HGNC:):

KYNU links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 11 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-142954375-CTTTTATAAAAGGTGTATTTTAATTTGATGTTAGAAACAACGAACTTTAAAAATGTAATTGGCCTTAATATCTTTTTAGATTCCTTTGAAGATATACTTAGCACAAAAATATGCTCCTTGGGAATTTGACAATTGAGCTGATAATAGGATATATCATTTTTAGTTTACAGGCAAAAGCAAATGCTTCATTATTTTGTTGTTATTTACTACATCATAAAAGAAATTTAATTTTAGCTAGCTGTGTGCATCTAAGTCCAGATATCATTTGATAAAATGAGTCAAGTGGGAAAACTTCCATTTCTTTGTGATGACACATCAAATATGCCCTTATCTCTAAAGACATTAAGAATGATTGAGTGAAGTCTTCCTACTTTGTTTTTTCAGTATCTTTAGACATAGTACAAACATCTAAATTACGATATGTTTATTTTACAGGAGCCAATGAGAAAGAAATAGCCCTAATGAATGCTTTGACTGTAAATTTACATCTTCTAATGGTAAGTTTTCTTTCCCACTAATGTTTAGAACACATTCATTTACAGAATCTGATGTTTTTCTATCTTTAATTCATGAGCTTCTGGGGGTTTACTTATTTAAAAATAAATTGTGAGGTTATTTTCATTTTTACTAGGAAATGCTGGACCATGATATAATAGCTTCTTCCTAATCATGGAAGAGTTGACTCTTGAGAAGAGCTTTAGAATAATGAACAGTTCTTGTCTGGGAAAATAAAGAATAAGAGCCATAATGGGTAAATAGGCAAACTACATGCAAGCCTACAAAACAGTGATGTACAATGCTAGCAAAGCACTGACCTTTTTGGAAAGACAATTTTCTAATGGCTTCAGCAGAGTGAGTTAGTGGA-C is Pathogenic according to our data. Variant chr2-142954375-CTTTTATAAAAGGTGTATTTTAATTTGATGTTAGAAACAACGAACTTTAAAAATGTAATTGGCCTTAATATCTTTTTAGATTCCTTTGAAGATATACTTAGCACAAAAATATGCTCCTTGGGAATTTGACAATTGAGCTGATAATAGGATATATCATTTTTAGTTTACAGGCAAAAGCAAATGCTTCATTATTTTGTTGTTATTTACTACATCATAAAAGAAATTTAATTTTAGCTAGCTGTGTGCATCTAAGTCCAGATATCATTTGATAAAATGAGTCAAGTGGGAAAACTTCCATTTCTTTGTGATGACACATCAAATATGCCCTTATCTCTAAAGACATTAAGAATGATTGAGTGAAGTCTTCCTACTTTGTTTTTTCAGTATCTTTAGACATAGTACAAACATCTAAATTACGATATGTTTATTTTACAGGAGCCAATGAGAAAGAAATAGCCCTAATGAATGCTTTGACTGTAAATTTACATCTTCTAATGGTAAGTTTTCTTTCCCACTAATGTTTAGAACACATTCATTTACAGAATCTGATGTTTTTCTATCTTTAATTCATGAGCTTCTGGGGGTTTACTTATTTAAAAATAAATTGTGAGGTTATTTTCATTTTTACTAGGAAATGCTGGACCATGATATAATAGCTTCTTCCTAATCATGGAAGAGTTGACTCTTGAGAAGAGCTTTAGAATAATGAACAGTTCTTGTCTGGGAAAATAAAGAATAAGAGCCATAATGGGTAAATAGGCAAACTACATGCAAGCCTACAAAACAGTGATGTACAATGCTAGCAAAGCACTGACCTTTTTGGAAAGACAATTTTCTAATGGCTTCAGCAGAGTGAGTTAGTGGA-C is described in ClinVar as [Pathogenic]. Clinvar id is 1695427.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KYNU	NM_003937.3 linkuse as main transcript	c.374-433_435+369del		exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant	5/14	ENST00000264170.9	NP_003928.1	Q16719-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000264170.9 linkuse as main transcript	c.374-433_435+369del		exon_loss_variant, splice_acceptor_variant, splice_donor_variant, splice_region_variant, intron_variant	5/14	1	NM_003937.3	ENSP00000264170.4		Q16719-1

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Vertebral, cardiac, renal, and limb defects syndrome 2

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Mar 06, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.