chr2-142918608-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePP5_Moderate
The NM_003937.3(KYNU):c.170-1G>T variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Consequence
NM_003937.3 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 5AN: 140558Hom.: 0 Cov.: 32 FAILED QC
GnomAD3 exomes AF: 0.000142 AC: 28AN: 197344Hom.: 0 AF XY: 0.000112 AC XY: 12AN XY: 106802
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000487 AC: 66AN: 1356608Hom.: 0 Cov.: 34 AF XY: 0.0000372 AC XY: 25AN XY: 672594
GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000356 AC: 5AN: 140626Hom.: 0 Cov.: 32 AF XY: 0.0000592 AC XY: 4AN XY: 67540
ClinVar
Submissions by phenotype
Vertebral, cardiac, renal, and limb defects syndrome 2 Pathogenic:1
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Congenital NAD deficiency disorder Pathogenic:1
This variant was discovered in a consanguineous family of Middle East origin. The patient presented multiple congenital malformations affecting vertebrae, heart, kidney among others. This variant is a protein truncating variant and novel (ExAC MAF 0). The patient is homozygous, while her unaffected parents and four unaffected siblings are either wildtype or heterozygous for this variant. Enzyme assay confirmed that the protein product of this gene variant has lost enzyme activity. Mouse embryos homozygous null for Kynu presented similar phenotype as observed in the patient, and also showed reduced concentration of NAD in the embryonic tissue. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at