rs1061248

Variant names:

• chr1-219968681-C-A
• rs1061248
• NM_004446.3:c.*125G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-219968681-C-A
• chr1-219968681-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004446.3(EPRS1):​c.*125G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 729,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000041 (0 hom.)
• Consequence: EPRS1 NM_004446.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 11 publications found

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

ACMG classification

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=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPRS1	NM_004446.3	c.*125G>T		3_prime_UTR_variant	Exon 32 of 32	ENST00000366923.8	NP_004437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPRS1	ENST00000366923.8	c.*125G>T		3_prime_UTR_variant	Exon 32 of 32	1	NM_004446.3	ENSP00000355890.3
EPRS1	ENST00000468487.1	n.*8G>T		downstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000411 AC: 3 AN: 729382 Hom.: 0 Cov.: 10 AF XY: 0.00000804 AC XY: 3 AN XY: 373010

African (AFR) AF: 0.00 AC: 0 AN: 18004

American (AMR) AF: 0.00 AC: 0 AN: 22912

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15954

East Asian (EAS) AF: 0.00 AC: 0 AN: 33940

South Asian (SAS) AF: 0.00 AC: 0 AN: 50118

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3208

European-Non Finnish (NFE) AF: 0.00000596 AC: 3 AN: 503608

Other (OTH) AF: 0.00 AC: 0 AN: 35220

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.40
PhyloP100		0.049
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1061248; hg19: chr1-220142023;