18-57601724-C-T

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

2

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]

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
NARS1NM_004539.4 linkc.1575G>A p.Thr525Thr synonymous_variant Exon 14 of 14 ENST00000256854.10 NP_004530.1 O43776-1
NARS1XM_005266700.3 linkc.1572G>A p.Thr524Thr synonymous_variant Exon 14 of 14 XP_005266757.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NARS1ENST00000256854.10 linkc.1575G>A p.Thr525Thr synonymous_variant Exon 14 of 14 1 NM_004539.4 ENSP00000256854.4 O43776-1
NARS1ENST00000586807.5 linkn.*755G>A non_coding_transcript_exon_variant Exon 12 of 12 2 ENSP00000464988.1 K7EJ19
NARS1ENST00000589314.1 linkn.655G>A non_coding_transcript_exon_variant Exon 3 of 3 5
NARS1ENST00000586807.5 linkn.*755G>A 3_prime_UTR_variant Exon 12 of 12 2 ENSP00000464988.1 K7EJ19

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152082
Hom.:
0
Cov.:
33
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:
58
AN:
249508
Hom.:
0
AF XY:
0.000230
AC XY:
31
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.:
1
Cov.:
31
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:
30
AN:
152200
Hom.:
0
Cov.:
33
AF XY:
0.000202
AC XY:
15
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.:
0
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.

Other links and lift over

dbSNP: rs375159897; hg19: chr18-55268956; COSMIC: COSV56877363; COSMIC: COSV56877363; API