Genetic Variant EPRS1:c.389-112T>C (chr1-220032638-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004446.3(EPRS1):c.389-112T>C variant causes a intron 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

EPRS1
NM_004446.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.726

Publications

5 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPRS1	NM_004446.3 link	c.389-112T>C		intron_variant	Intron 4 of 31	ENST00000366923.8	NP_004437.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
EPRS1	ENST00000366923.8 link	c.389-112T>C	intron_variant	Intron 4 of 31	1	NM_004446.3	ENSP00000355890.3
EPRS1	ENST00000609181.5 link	c.389-112T>C	intron_variant	Intron 4 of 20	1		ENSP00000477245.1
EPRS1	ENST00000477030.2 link	n.389-112T>C	intron_variant	Intron 4 of 11	1		ENSP00000477493.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

862742

Hom.:

AF XY:

0.00

AC XY:

AN XY:

451656

African (AFR)

AF:

0.00

AC:

AN:

19906

American (AMR)

AF:

0.00

AC:

AN:

32174

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21484

East Asian (EAS)

AF:

0.00

AC:

AN:

36286

South Asian (SAS)

AF:

0.00

AC:

AN:

67812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40382

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4244

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

599966

Other (OTH)

AF:

0.00

AC:

AN:

40488

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.6

(source)

DANN

Benign

0.25

PhyloP100

0.73

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

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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