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GeneBe

rs6743085

Positions:

Variant summary

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

The NM_003937.3(KYNU):​c.585G>A​(p.Gly195=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.001 in 1,613,132 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00054 ( 9 hom. )

Consequence

KYNU
NM_003937.3 splice_region, synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.490
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=-0.52).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-142960626-G-A is Benign according to our data. Variant chr2-142960626-G-A is described in ClinVar as [Benign]. Clinvar id is 711853.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=-0.49 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 = 0.00538 (818/152110) while in subpopulation AFR AF= 0.0188 (781/41476). AF 95% confidence interval is 0.0177. There are 6 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 32. 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 GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
KYNUNM_003937.3 linkuse as main transcriptc.585G>A p.Gly195= splice_region_variant, synonymous_variant 8/14 ENST00000264170.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
KYNUENST00000264170.9 linkuse as main transcriptc.585G>A p.Gly195= splice_region_variant, synonymous_variant 8/141 NM_003937.3 P1Q16719-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00535
AC:
813
AN:
151992
Hom.:
7
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0188
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00184
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:
0.0000147
Gnomad OTH
AF:
0.00382
GnomAD3 exomes
AF:
0.00140
AC:
352
AN:
250950
Hom.:
2
AF XY:
0.000907
AC XY:
123
AN XY:
135622
show subpopulations
Gnomad AFR exome
AF:
0.0197
Gnomad AMR exome
AF:
0.000608
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000441
Gnomad OTH exome
AF:
0.000327
GnomAD4 exome
AF:
0.000544
AC:
795
AN:
1461022
Hom.:
9
Cov.:
30
AF XY:
0.000455
AC XY:
331
AN XY:
726850
show subpopulations
Gnomad4 AFR exome
AF:
0.0196
Gnomad4 AMR exome
AF:
0.000693
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000207
Gnomad4 OTH exome
AF:
0.00133
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00538
AC:
818
AN:
152110
Hom.:
6
Cov.:
32
AF XY:
0.00500
AC XY:
372
AN XY:
74364
show subpopulations
Gnomad4 AFR
AF:
0.0188
Gnomad4 AMR
AF:
0.00183
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00378
Alfa
AF:
0.00130
Hom.:
6
Bravo
AF:
0.00636
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

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
-0.52
CADD
Benign
5.5
DANN
Benign
0.69

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: rs6743085; hg19: chr2-143718195; API