rs2230301

Positions:

• chr1-220024283-G-C
• chr1-220024283-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 14/21 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 same amino acid change has been previously reported as Benignin ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPRS1 NM_004446.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 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/exons	MANE	Protein	UniProt
EPRS1	NM_004446.3	c.924C>G	p.Asp308Glu	missense_variant	8/32	ENST00000366923.8	NP_004437.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPRS1	ENST00000366923.8	c.924C>G	p.Asp308Glu	missense_variant	8/32	1	NM_004446.3	ENSP00000355890.3
EPRS1	ENST00000609181.5	c.924C>G	p.Asp308Glu	missense_variant	8/21	1		ENSP00000477245.1
EPRS1	ENST00000477030.2	n.*244C>G		non_coding_transcript_exon_variant	7/12	1		ENSP00000477493.1
EPRS1	ENST00000477030.2	n.*244C>G		3_prime_UTR_variant	7/12	1		ENSP00000477493.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1443140 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 717876

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

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	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.25
DANN	Benign	0.17
DEOGEN2	Benign	0.22	T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.081	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.69	N;.
PrimateAI	Uncertain	0.49	T
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	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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

Other links and lift over

dbSNP: rs2230301; hg19: chr1-220197625;