rs201447520

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_002047.4(GARS1):c.765G>A(p.Ala255Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000794 in 1,612,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000078 ( 0 hom. )

Consequence

GARS1
NM_002047.4 synonymous

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:5

Conservation

PhyloP100: -1.45

Variant links:

Genes affected

GARS1 (HGNC:4162): (glycyl-tRNA synthetase 1) This gene encodes glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids. The encoded enzyme is an (alpha)2 dimer which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

GARS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 7-30609614-G-A is Benign according to our data. Variant chr7-30609614-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 360006.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=5, Uncertain_significance=1}.

BP7

Synonymous conserved (PhyloP=-1.45 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0000922 (14/151918) while in subpopulation EAS AF= 0.000193 (1/5186). AF 95% confidence interval is 0.0000117. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.765G>A	p.Ala255Ala	synonymous_variant	Exon 7 of 17	ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 link	c.603G>A	p.Ala201Ala	synonymous_variant	Exon 7 of 17		NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266.8 link	c.765G>A	p.Ala255Ala	synonymous_variant	Exon 7 of 17	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 link	c.765G>A	p.Ala255Ala	synonymous_variant	Exon 7 of 17			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 link	c.663G>A	p.Ala221Ala	synonymous_variant	Exon 6 of 16			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693.1 link	c.597G>A	p.Ala199Ala	synonymous_variant	Exon 8 of 18			ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000675051.1 link	c.564G>A	p.Ala188Ala	synonymous_variant	Exon 7 of 17			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674815.1 link	c.396G>A	p.Ala132Ala	synonymous_variant	Exon 7 of 17			ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 link	c.396G>A	p.Ala132Ala	synonymous_variant	Exon 8 of 18			ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 link	n.765G>A		non_coding_transcript_exon_variant	Exon 7 of 18	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 link	n.*479G>A		non_coding_transcript_exon_variant	Exon 8 of 18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.765G>A		non_coding_transcript_exon_variant	Exon 7 of 17			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.*103G>A		non_coding_transcript_exon_variant	Exon 8 of 18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 link	n.765G>A		non_coding_transcript_exon_variant	Exon 7 of 16			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 link	n.*635G>A		non_coding_transcript_exon_variant	Exon 8 of 18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 link	n.765G>A		non_coding_transcript_exon_variant	Exon 7 of 15			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 link	n.*707G>A		non_coding_transcript_exon_variant	Exon 9 of 19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.765G>A		non_coding_transcript_exon_variant	Exon 7 of 17			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 link	n.*216G>A		non_coding_transcript_exon_variant	Exon 7 of 17			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 link	n.*54G>A		non_coding_transcript_exon_variant	Exon 8 of 18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.*197G>A		non_coding_transcript_exon_variant	Exon 7 of 17			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 link	n.765G>A		non_coding_transcript_exon_variant	Exon 7 of 16			ENSP00000502681.1	A0A6Q8PHI7
GARS1	ENST00000674616.1 link	n.*479G>A		3_prime_UTR_variant	Exon 8 of 18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674737.1 link	n.*103G>A		3_prime_UTR_variant	Exon 8 of 18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000675529.1 link	n.*635G>A		3_prime_UTR_variant	Exon 8 of 18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000676088.1 link	n.*707G>A		3_prime_UTR_variant	Exon 9 of 19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676164.1 link	n.*216G>A		3_prime_UTR_variant	Exon 7 of 17			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 link	n.*54G>A		3_prime_UTR_variant	Exon 8 of 18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.*197G>A		3_prime_UTR_variant	Exon 7 of 17			ENSP00000501980.1	A0A6Q8PFU7

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000802

AC:

AN:

249420

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135336

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.000894

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000795

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000780

AC:

114

AN:

1460972

Hom.:

Cov.:

AF XY:

0.0000825

AC XY:

AN XY:

726858

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.000957

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000657

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000922

AC:

AN:

151918

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74194

show subpopulations

Gnomad4 AFR

AF:

0.0000484

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000149

Hom.:

Bravo

AF:

0.0000529

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:5

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 2D

Uncertain:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not specified

Benign:1

Jul 11, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Distal spinal muscular atrophy

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Charcot-Marie-Tooth disease type 2

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Sep 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Neuronopathy, distal hereditary motor, type 5A

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

7.6

DANN

Benign

0.44

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