Variant 1-54758004-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_152268.4(PARS2):c.1158C>T(p.Ala386=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,614,174 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

PARS2
NM_152268.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.787

Variant links:

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]

PARS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-54758004-G-A is Benign according to our data. Variant chr1-54758004-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 381172.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.787 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PARS2	NM_152268.4 linkuse as main transcript	c.1158C>T	p.Ala386=	synonymous_variant	2/2	ENST00000371279.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PARS2	ENST00000371279.4 linkuse as main transcript	c.1158C>T	p.Ala386=	synonymous_variant	2/2	1	NM_152268.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00105

AC:

160

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00131

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00113

AC:

283

AN:

251346

Hom.:

AF XY:

0.00113

AC XY:

154

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00200

Gnomad ASJ exome

AF:

0.00536

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00114

Gnomad OTH exome

AF:

0.00179

GnomAD4 exome

AF:

0.00112

AC:

1632

AN:

1461860

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

804

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00221

Gnomad4 ASJ exome

AF:

0.00551

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000417

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00113

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00105

AC:

160

AN:

152314

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00547

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00131

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00105

Hom.:

Bravo

AF:

0.00108

EpiCase

AF:

0.00115

EpiControl

AF:

0.00148

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 13, 2023	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2021	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jan 01, 2024	PARS2: BP4, BP7 -

PARS2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 19, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.30

DANN

Benign

0.44

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over