rs1180947

chr1-54763681-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152268.4(PARS2):c.-30+780T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0266 in 152,338 control chromosomes in the GnomAD database, including 100 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 0.027 (100 hom., cov: 33)
• Consequence: PARS2 NM_152268.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.710

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0266 (4051/152338) while in subpopulation SAS AF= 0.0435 (210/4830). AF 95% confidence interval is 0.0387. There are 100 homozygotes in gnomad4. There are 1927 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 100 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARS2	NM_152268.4	c.-30+780T>C		intron_variant		ENST00000371279.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARS2	ENST00000371279.4	c.-30+780T>C		intron_variant		1	NM_152268.4	P1

Frequencies

GnomAD3 genomes AF: 0.0266 AC: 4055 AN: 152220 Hom.: 100 Cov.: 33

Gnomad AFR AF: 0.00673

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0402

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0266 AC: 4051 AN: 152338 Hom.: 100 Cov.: 33 AF XY: 0.0259 AC XY: 1927 AN XY: 74498

Gnomad4 AFR AF: 0.00671

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0397

Gnomad4 OTH AF: 0.0402

Alfa AF: 0.0329 Hom.: 29

Bravo AF: 0.0248

Asia WGS AF: 0.0190 AC: 66 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.74
Dann	Benign	0.24

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: rs1180947; hg19: chr1-55229354;