dbSNP rs2230301: EPRS1:p.Asp308Glu (chr1-220024283-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004446.3(EPRS1):c.924C>G(p.Asp308Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPRS1
NM_004446.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.344

Publications

39 publications found

Variant links:

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]

EPRS1 Gene-Disease associations (from GenCC):

leukodystrophy, hypomyelinating, 15
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P

EPRS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08087841).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPRS1	NM_004446.3 link	c.924C>G	p.Asp308Glu	missense_variant	Exon 8 of 32	ENST00000366923.8	NP_004437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
EPRS1	ENST00000366923.8 link	c.924C>G	p.Asp308Glu	missense_variant	Exon 8 of 32	1	NM_004446.3	ENSP00000355890.3
EPRS1	ENST00000609181.5 link	c.924C>G	p.Asp308Glu	missense_variant	Exon 8 of 21	1		ENSP00000477245.1
EPRS1	ENST00000477030.2 link	n.*244C>G		non_coding_transcript_exon_variant	Exon 7 of 12	1		ENSP00000477493.1
EPRS1	ENST00000477030.2 link	n.*244C>G		3_prime_UTR_variant	Exon 7 of 12	1		ENSP00000477493.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1443140

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

717876

African (AFR)

AF:

0.00

AC:

AN:

32264

American (AMR)

AF:

0.00

AC:

AN:

38970

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25170

East Asian (EAS)

AF:

0.00

AC:

AN:

39550

South Asian (SAS)

AF:

0.00

AC:

AN:

82244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106516

Other (OTH)

AF:

0.00

AC:

AN:

59616

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.25

(source)

DANN

Benign

0.17

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0040

MetaRNN

Benign

0.081

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-0.69

N;.

PhyloP100

0.34

PrimateAI

Uncertain

0.49

PROVEAN

Benign

1.2

N;.

REVEL

Benign

0.22

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;.

Polyphen

0.0

B;.

Vest4

0.043

MutPred

0.32

Loss of MoRF binding (P = 0.1162);Loss of MoRF binding (P = 0.1162);

MVP

0.11

MPC

0.60

ClinPred

0.075

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.057

gMVP

0.22

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over