rs561670727
Positions:
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS1
The NM_001605.3(AARS1):āc.846A>Gā(p.Lys282Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000483 in 1,614,094 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.000033 ( 0 hom., cov: 31)
Exomes š: 0.000050 ( 1 hom. )
Consequence
AARS1
NM_001605.3 synonymous
NM_001605.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.317
Genes affected
AARS1 (HGNC:20): (alanyl-tRNA synthetase 1) The human alanyl-tRNA synthetase (AARS) belongs to a family of tRNA synthases, of the class II enzymes. Class II tRNA synthases evolved early in evolution and are highly conserved. This is reflected by the fact that 498 of the 968-residue polypeptide human AARS shares 41% identity witht the E.coli protein. tRNA synthases are the enzymes that interpret the RNA code and attach specific aminoacids to the tRNAs that contain the cognate trinucleotide anticodons. They consist of a catalytic domain which interacts with the amino acid acceptor-T psi C helix of the tRNA, and a second domain which interacts with the rest of the tRNA structure. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
Variant 16-70269734-T-C is Benign according to our data. Variant chr16-70269734-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 476744.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.317 with no splicing effect.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000328 (5/152208) while in subpopulation SAS AF= 0.00104 (5/4818). AF 95% confidence interval is 0.000409. There are 0 homozygotes in gnomad4. There are 4 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
AARS1 | NM_001605.3 | c.846A>G | p.Lys282Lys | synonymous_variant | 7/21 | ENST00000261772.13 | NP_001596.2 | |
AARS1 | XM_047433666.1 | c.846A>G | p.Lys282Lys | synonymous_variant | 7/16 | XP_047289622.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
AARS1 | ENST00000261772.13 | c.846A>G | p.Lys282Lys | synonymous_variant | 7/21 | 1 | NM_001605.3 | ENSP00000261772.8 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152090Hom.: 0 Cov.: 31
GnomAD3 genomes
AF:
AC:
5
AN:
152090
Hom.:
Cov.:
31
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: 0.0000954 AC: 24AN: 251476Hom.: 0 AF XY: 0.0000957 AC XY: 13AN XY: 135910
GnomAD3 exomes
AF:
AC:
24
AN:
251476
Hom.:
AF XY:
AC XY:
13
AN XY:
135910
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: 0.0000499 AC: 73AN: 1461886Hom.: 1 Cov.: 35 AF XY: 0.0000715 AC XY: 52AN XY: 727242
GnomAD4 exome
AF:
AC:
73
AN:
1461886
Hom.:
Cov.:
35
AF XY:
AC XY:
52
AN XY:
727242
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: 0.0000328 AC: 5AN: 152208Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74400
GnomAD4 genome
AF:
AC:
5
AN:
152208
Hom.:
Cov.:
31
AF XY:
AC XY:
4
AN XY:
74400
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
Asia WGS
AF:
AC:
2
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 27, 2023 | - - |
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