17-42956310-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001261434.2(AARSD1):c.557G>A(p.Arg186Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000011 ( 0 hom. )
Consequence
AARSD1
NM_001261434.2 missense
NM_001261434.2 missense
Scores
5
8
5
Clinical Significance
Conservation
PhyloP100: 4.81
Genes affected
AARSD1 (HGNC:28417): (alanyl-tRNA synthetase domain containing 1) Predicted to enable Ser-tRNA(Ala) hydrolase activity. Predicted to be involved in regulation of translational fidelity. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.33565515).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AARSD1 | NM_001261434.2 | c.557G>A | p.Arg186Gln | missense_variant | 6/12 | ENST00000427569.7 | |
PTGES3L-AARSD1 | NM_001136042.2 | c.1079G>A | p.Arg360Gln | missense_variant | 11/17 | ||
PTGES3L-AARSD1 | NM_025267.4 | c.896G>A | p.Arg299Gln | missense_variant | 11/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AARSD1 | ENST00000427569.7 | c.557G>A | p.Arg186Gln | missense_variant | 6/12 | 5 | NM_001261434.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152118Hom.: 0 Cov.: 31
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251468Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135916
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GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461878Hom.: 0 Cov.: 34 AF XY: 0.00000963 AC XY: 7AN XY: 727246
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152118Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74314
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 31, 2023 | The c.1079G>A (p.R360Q) alteration is located in exon 11 (coding exon 11) of the AARSD1 gene. This alteration results from a G to A substitution at nucleotide position 1079, causing the arginine (R) at amino acid position 360 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;.;.;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;.;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationAssessor
Pathogenic
H;.;.;.;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;N;D;D;D;D
REVEL
Uncertain
Sift
Uncertain
D;T;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;.;.;.;D;.
Vest4
MutPred
0.45
.;.;.;.;Gain of helix (P = 0.062);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at