NM_004446.3:c.*125G>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004446.3(EPRS1):​c.*125G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 879,570 control chromosomes in the GnomAD database, including 99,194 homozygotes. 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: 𝑓 0.46 (16212 hom., cov: 33)
  • Exomes 𝑓: 0.48 (82982 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004446.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPRS1	NM_004446.3	MANE Select	c.*125G>A		3_prime_UTR	Exon 32 of 32	NP_004437.2	P07814

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EPRS1	ENST00000366923.8	TSL:1 MANE Select	c.*125G>A		3_prime_UTR	Exon 32 of 32	ENSP00000355890.3	P07814
	EPRS1	ENST00000927912.1		c.*125G>A		3_prime_UTR	Exon 33 of 33	ENSP00000597971.1
	EPRS1	ENST00000927914.1		c.*125G>A		3_prime_UTR	Exon 33 of 33	ENSP00000597973.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 69960 AN: 151910 Hom.: 16206 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.522

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.467

GnomAD4 exome AF: 0.476 AC: 345987 AN: 727544 Hom.: 82982 Cov.: 10 AF XY: 0.476 AC XY: 177001 AN XY: 372080

African (AFR) AF: 0.416 AC: 7477 AN: 17966

American (AMR) AF: 0.385 AC: 8802 AN: 22872

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 7687 AN: 15932

East Asian (EAS) AF: 0.480 AC: 16273 AN: 33900

South Asian (SAS) AF: 0.523 AC: 26122 AN: 49994

European-Finnish (FIN) AF: 0.534 AC: 24743 AN: 46328

Middle Eastern (MID) AF: 0.393 AC: 1257 AN: 3196

European-Non Finnish (NFE) AF: 0.472 AC: 237109 AN: 502218

Other (OTH) AF: 0.470 AC: 16517 AN: 35138

GnomAD4 genome AF: 0.460 AC: 70003 AN: 152026 Hom.: 16212 Cov.: 33 AF XY: 0.464 AC XY: 34502 AN XY: 74320

African (AFR) AF: 0.426 AC: 17643 AN: 41462

American (AMR) AF: 0.412 AC: 6281 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3468

East Asian (EAS) AF: 0.521 AC: 2693 AN: 5166

South Asian (SAS) AF: 0.524 AC: 2530 AN: 4826

European-Finnish (FIN) AF: 0.548 AC: 5790 AN: 10564

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31894 AN: 67970

Other (OTH) AF: 0.464 AC: 979 AN: 2108

Alfa AF: 0.454 Hom.: 4394

Bravo AF: 0.447

Asia WGS AF: 0.549 AC: 1911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.8
DANN	Benign	0.37
PhyloP100		0.049
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV65097269; COSMIC: COSV65097269;