chr16-75627862-C-T
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_005548.3(KARS1):c.*33G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00929 in 1,212,610 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0083 ( 19 hom., cov: 33)
Exomes 𝑓: 0.0094 ( 82 hom. )
Consequence
KARS1
NM_005548.3 3_prime_UTR
NM_005548.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.473
Genes affected
KARS1 (HGNC:6215): (lysyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 16-75627862-C-T is Benign according to our data. Variant chr16-75627862-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1218463.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0083 (1264/152298) while in subpopulation NFE AF= 0.00944 (642/68022). AF 95% confidence interval is 0.00883. There are 19 homozygotes in gnomad4. There are 660 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 19 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KARS1 | NM_005548.3 | c.*33G>A | 3_prime_UTR_variant | 14/14 | ENST00000302445.8 | ||
KARS1 | NM_001130089.2 | c.*33G>A | 3_prime_UTR_variant | 15/15 | |||
KARS1 | NM_001378148.1 | c.*33G>A | 3_prime_UTR_variant | 14/14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KARS1 | ENST00000302445.8 | c.*33G>A | 3_prime_UTR_variant | 14/14 | 1 | NM_005548.3 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00831 AC: 1264AN: 152180Hom.: 19 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
1264
AN:
152180
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00947 AC: 2379AN: 251294Hom.: 21 AF XY: 0.00956 AC XY: 1299AN XY: 135844
GnomAD3 exomes
AF:
AC:
2379
AN:
251294
Hom.:
AF XY:
AC XY:
1299
AN XY:
135844
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00943 AC: 9999AN: 1060312Hom.: 82 Cov.: 15 AF XY: 0.00914 AC XY: 4991AN XY: 546128
GnomAD4 exome
AF:
AC:
9999
AN:
1060312
Hom.:
Cov.:
15
AF XY:
AC XY:
4991
AN XY:
546128
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00830 AC: 1264AN: 152298Hom.: 19 Cov.: 33 AF XY: 0.00886 AC XY: 660AN XY: 74476
GnomAD4 genome
?
AF:
AC:
1264
AN:
152298
Hom.:
Cov.:
33
AF XY:
AC XY:
660
AN XY:
74476
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
11
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at