1-220024283-G-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004446.3(EPRS1):c.924C>A(p.Asp308Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 1,594,018 control chromosomes in the GnomAD database, including 544,784 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.86 ( 57253 hom., cov: 34)

Exomes 𝑓: 0.82 ( 487531 hom. )

Consequence

EPRS1
NM_004446.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.344

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2932273E-6).

BP6

Variant 1-220024283-G-T is Benign according to our data. Variant chr1-220024283-G-T is described in ClinVar as [Benign]. Clinvar id is 1166609.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPRS1	NM_004446.3 link	c.924C>A	p.Asp308Glu	missense_variant	Exon 8 of 32	ENST00000366923.8	NP_004437.2	P07814

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
EPRS1	ENST00000366923.8 link	c.924C>A	p.Asp308Glu	missense_variant	Exon 8 of 32	1	NM_004446.3	ENSP00000355890.3	P07814
EPRS1	ENST00000609181.5 link	c.924C>A	p.Asp308Glu	missense_variant	Exon 8 of 21	1		ENSP00000477245.1	V9GYZ6
EPRS1	ENST00000477030.2 link	n.*244C>A		non_coding_transcript_exon_variant	Exon 7 of 12	1		ENSP00000477493.1	V9GZ76
EPRS1	ENST00000477030.2 link	n.*244C>A		3_prime_UTR_variant	Exon 7 of 12	1		ENSP00000477493.1	V9GZ76

Frequencies

GnomAD3 genomes

AF:

0.864

AC:

131431

AN:

152130

Hom.:

57200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.967

Gnomad AMI

AF:

0.776

Gnomad AMR

AF:

0.874

Gnomad ASJ

AF:

0.748

Gnomad EAS

AF:

0.932

Gnomad SAS

AF:

0.849

Gnomad FIN

AF:

0.817

Gnomad MID

AF:

0.813

Gnomad NFE

AF:

0.810

Gnomad OTH

AF:

0.847

GnomAD3 exomes

AF:

0.842

AC:

197162

AN:

234180

Hom.:

83434

AF XY:

0.835

AC XY:

105766

AN XY:

126702

show subpopulations

Gnomad AFR exome

AF:

0.970

Gnomad AMR exome

AF:

0.909

Gnomad ASJ exome

AF:

0.742

Gnomad EAS exome

AF:

0.935

Gnomad SAS exome

AF:

0.837

Gnomad FIN exome

AF:

0.817

Gnomad NFE exome

AF:

0.805

Gnomad OTH exome

AF:

0.830

GnomAD4 exome

AF:

0.821

AC:

1183923

AN:

1441770

Hom.:

487531

Cov.:

AF XY:

0.820

AC XY:

588200

AN XY:

717234

show subpopulations

Gnomad4 AFR exome

AF:

0.974

Gnomad4 AMR exome

AF:

0.904

Gnomad4 ASJ exome

AF:

0.751

Gnomad4 EAS exome

AF:

0.926

Gnomad4 SAS exome

AF:

0.838

Gnomad4 FIN exome

AF:

0.822

Gnomad4 NFE exome

AF:

0.810

Gnomad4 OTH exome

AF:

0.825

GnomAD4 genome

AF:

0.864

AC:

131541

AN:

152248

Hom.:

57253

Cov.:

AF XY:

0.864

AC XY:

64285

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.967

Gnomad4 AMR

AF:

0.874

Gnomad4 ASJ

AF:

0.748

Gnomad4 EAS

AF:

0.932

Gnomad4 SAS

AF:

0.847

Gnomad4 FIN

AF:

0.817

Gnomad4 NFE

AF:

0.810

Gnomad4 OTH

AF:

0.848

Alfa

AF:

0.816

Hom.:

124282

Bravo

AF:

0.873

TwinsUK

AF:

0.816

AC:

3024

ALSPAC

AF:

0.814

AC:

3137

ESP6500AA

AF:

0.957

AC:

4216

ESP6500EA

AF:

0.809

AC:

6957

ExAC

AF:

0.844

AC:

102427

Asia WGS

AF:

0.911

AC:

3167

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Leukodystrophy, hypomyelinating, 15

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.055

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.24

DANN

Benign

0.21

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.33

T;T

MetaRNN

Benign

0.0000013

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.69

N;.

PrimateAI

Uncertain

0.49

PROVEAN

Benign

1.2

N;.

REVEL

Benign

0.21

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);

MPC

0.60

ClinPred

0.00069

GERP RS

-1.6

Varity_R

0.057

gMVP

0.22

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over