Genetic Variant NARS1:p.Thr525Thr (chr18-57601724-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6_ModerateBP7

The NM_004539.4(NARS1):c.1575G>A(p.Thr525Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,613,316 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 0.00020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 1 hom. )

Consequence

NARS1
NM_004539.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.161

Variant links:

Genes affected

NARS1 (HGNC:7643): (asparaginyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Asparaginyl-tRNA synthetase is localized to the cytoplasm and belongs to the class II family of tRNA synthetases. The N-terminal domain represents the signature sequence for the eukaryotic asparaginyl-tRNA synthetases. [provided by RefSeq, Jul 2008]

NARS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 18-57601724-C-T is Benign according to our data. Variant chr18-57601724-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2648746.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.161 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NARS1	NM_004539.4 link	c.1575G>A	p.Thr525Thr	synonymous_variant	Exon 14 of 14	ENST00000256854.10	NP_004530.1	O43776-1
NARS1	XM_005266700.3 link	c.1572G>A	p.Thr524Thr	synonymous_variant	Exon 14 of 14		XP_005266757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NARS1	ENST00000256854.10 link	c.1575G>A	p.Thr525Thr	synonymous_variant	Exon 14 of 14	1	NM_004539.4	ENSP00000256854.4	O43776-1
NARS1	ENST00000586807.5 link	n.*755G>A		non_coding_transcript_exon_variant	Exon 12 of 12	2		ENSP00000464988.1	K7EJ19
NARS1	ENST00000589314.1 link	n.655G>A		non_coding_transcript_exon_variant	Exon 3 of 3	5
NARS1	ENST00000586807.5 link	n.*755G>A		3_prime_UTR_variant	Exon 12 of 12	2		ENSP00000464988.1	K7EJ19

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000232

AC:

AN:

249508

Hom.:

AF XY:

0.000230

AC XY:

AN XY:

135064

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00318

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000170

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000307

AC:

448

AN:

1461116

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

232

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00478

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000265

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000197

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000445

Hom.:

Bravo

AF:

0.000276

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

NARS1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.2

DANN

Benign

0.80

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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