rs763737931
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_004446.3(EPRS1):c.1015C>T(p.Arg339Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
EPRS1
NM_004446.3 stop_gained
NM_004446.3 stop_gained
Scores
2
4
1
Clinical Significance
Conservation
PhyloP100: 2.60
Genes affected
EPRS1 (HGNC:3418): (glutamyl-prolyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a multifunctional aminoacyl-tRNA synthetase that catalyzes the aminoacylation of glutamic acid and proline tRNA species. Alternative splicing has been observed for this gene, but the full-length nature and biological validity of the variant have not been determined. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 1-220022447-G-A is Pathogenic according to our data. Variant chr1-220022447-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 523134.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EPRS1 | NM_004446.3 | c.1015C>T | p.Arg339Ter | stop_gained | 9/32 | ENST00000366923.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EPRS1 | ENST00000366923.8 | c.1015C>T | p.Arg339Ter | stop_gained | 9/32 | 1 | NM_004446.3 | P1 | |
EPRS1 | ENST00000609181.5 | c.1015C>T | p.Arg339Ter | stop_gained | 9/21 | 1 | |||
EPRS1 | ENST00000477030.2 | c.*335C>T | 3_prime_UTR_variant, NMD_transcript_variant | 8/12 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251332Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135830
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GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461674Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727158
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Leukodystrophy, hypomyelinating, 15 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Aug 20, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
A
Vest4
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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