1-54757495-A-C

Position:

• chr1-54757495-A-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_152268.4(PARS2):​c.*239T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0158 in 409,680 control chromosomes in the GnomAD database, including 386 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (74 hom., cov: 32)
  • Exomes 𝑓: 0.018 (312 hom.)
• Consequence: PARS2 NM_152268.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.355

Genes affected

PARS2 (HGNC:30563): (prolyl-tRNA synthetase 2, mitochondrial) This gene encodes a putative member of the class II family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. This protein is encoded by the nuclear genome but is likely to be imported to the mitochondrion where it is thought to catalyze the ligation of proline to tRNA molecules. Mutations have been found in this gene in some patients with Alpers syndrome. [provided by RefSeq, Mar 2015]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-54757495-A-C is Benign according to our data. Variant chr1-54757495-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 1189621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARS2	NM_152268.4	c.*239T>G		3_prime_UTR_variant	2/2	ENST00000371279.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARS2	ENST00000371279.4	c.*239T>G		3_prime_UTR_variant	2/2	1	NM_152268.4	P1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1762 AN: 152198 Hom.: 73 Cov.: 32

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00314

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00671

GnomAD4 exome AF: 0.0183 AC: 4703 AN: 257364 Hom.: 312 Cov.: 0 AF XY: 0.0209 AC XY: 2778 AN XY: 132920

Gnomad4 AFR exome AF: 0.0134

Gnomad4 AMR exome AF: 0.00181

Gnomad4 ASJ exome AF: 0.00221

Gnomad4 EAS exome AF: 0.143

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0000578

Gnomad4 NFE exome AF: 0.000216

Gnomad4 OTH exome AF: 0.00861

GnomAD4 genome AF: 0.0116 AC: 1768 AN: 152316 Hom.: 74 Cov.: 32 AF XY: 0.0132 AC XY: 986 AN XY: 74492

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.00314

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00996

Alfa AF: 0.00534 Hom.: 0

Bravo AF: 0.00932

Asia WGS AF: 0.109 AC: 377 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.8
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs74467041; hg19: chr1-55223168;