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GeneBe

2-142885490-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_003937.3(KYNU):c.123C>T(p.His41=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,930 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0096 ( 26 hom., cov: 29)
Exomes 𝑓: 0.0012 ( 24 hom. )

Consequence

KYNU
NM_003937.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.566
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-142885490-C-T is Benign according to our data. Variant chr2-142885490-C-T is described in ClinVar as [Benign]. Clinvar id is 785012.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.566 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00962 (1464/152220) while in subpopulation AFR AF= 0.0328 (1362/41524). AF 95% confidence interval is 0.0314. There are 26 homozygotes in gnomad4. There are 706 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 26 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KYNUNM_003937.3 linkuse as main transcriptc.123C>T p.His41= synonymous_variant 2/14 ENST00000264170.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KYNUENST00000264170.9 linkuse as main transcriptc.123C>T p.His41= synonymous_variant 2/141 NM_003937.3 P1Q16719-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00959
AC:
1459
AN:
152102
Hom.:
26
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.0328
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00419
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000294
Gnomad OTH
AF:
0.00718
GnomAD3 exomes
AF:
0.00259
AC:
652
AN:
251468
Hom.:
17
AF XY:
0.00202
AC XY:
274
AN XY:
135918
show subpopulations
Gnomad AFR exome
AF:
0.0330
Gnomad AMR exome
AF:
0.00179
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.000369
Gnomad OTH exome
AF:
0.00130
GnomAD4 exome
AF:
0.00121
AC:
1762
AN:
1461710
Hom.:
24
Cov.:
31
AF XY:
0.00105
AC XY:
762
AN XY:
727136
show subpopulations
Gnomad4 AFR exome
AF:
0.0339
Gnomad4 AMR exome
AF:
0.00199
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000464
Gnomad4 FIN exome
AF:
0.0000562
Gnomad4 NFE exome
AF:
0.000337
Gnomad4 OTH exome
AF:
0.00242
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00962
AC:
1464
AN:
152220
Hom.:
26
Cov.:
29
AF XY:
0.00949
AC XY:
706
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.0328
Gnomad4 AMR
AF:
0.00425
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000294
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00396
Hom.:
5
Bravo
AF:
0.0111
Asia WGS
AF:
0.000577
AC:
2
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000474

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.56
Cadd
Benign
3.3
Dann
Benign
0.24

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs16858205; hg19: chr2-143643059; API