2-142885488-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1

The NM_003937.3(KYNU):​c.121C>T​(p.His41Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,613,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. H41H) has been classified as Benign.

Frequency

Genomes: 𝑓 0.00069 ( 0 hom., cov: 29)
Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

KYNU
NM_003937.3 missense

Scores

3
16

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.851
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 2-142885488-C-T is Benign according to our data. Variant chr2-142885488-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 727204.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00069 (105/152260) while in subpopulation AFR AF= 0.0025 (104/41534). AF 95% confidence interval is 0.00211. There are 0 homozygotes in gnomad4. There are 47 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KYNUNM_003937.3 linkc.121C>T p.His41Tyr missense_variant Exon 2 of 14 ENST00000264170.9 NP_003928.1 Q16719-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KYNUENST00000264170.9 linkc.121C>T p.His41Tyr missense_variant Exon 2 of 14 1 NM_003937.3 ENSP00000264170.4 Q16719-1

Frequencies

GnomAD3 genomes
AF:
0.000690
AC:
105
AN:
152142
Hom.:
0
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.00251
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000155
AC:
39
AN:
251472
Hom.:
0
AF XY:
0.000132
AC XY:
18
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00228
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000561
AC:
82
AN:
1461718
Hom.:
0
Cov.:
31
AF XY:
0.0000509
AC XY:
37
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.00221
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.000690
AC:
105
AN:
152260
Hom.:
0
Cov.:
29
AF XY:
0.000631
AC XY:
47
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.00250
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.000454
Hom.:
0
Bravo
AF:
0.000650
ESP6500AA
AF:
0.00318
AC:
14
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000222
AC:
27

ClinVar

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

Submissions by phenotype

not provided Benign:1
Oct 02, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
17
DANN
Benign
0.97
DEOGEN2
Benign
0.21
T;.;T;T;.
Eigen
Benign
-0.15
Eigen_PC
Benign
-0.055
FATHMM_MKL
Benign
0.59
D
LIST_S2
Uncertain
0.95
.;D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.011
T;T;T;T;T
MetaSVM
Benign
-0.85
T
MutationAssessor
Uncertain
2.3
M;M;M;.;.
PrimateAI
Benign
0.42
T
PROVEAN
Uncertain
-2.9
D;D;D;D;.
REVEL
Benign
0.13
Sift
Benign
1.0
T;T;T;T;.
Sift4G
Benign
0.36
T;T;T;T;T
Polyphen
0.0020
B;.;B;.;.
Vest4
0.26
MVP
0.61
MPC
0.039
ClinPred
0.043
T
GERP RS
4.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.24
Details are displayed if max score is > 0.2
DS_DG_spliceai
0.24
Position offset: -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: rs146238174; hg19: chr2-143643057; API