Variant 7-30594966-TCTG-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP3BP6_ModerateBS1BS2

The NM_002047.4(GARS1):c.59_61del(p.Leu20del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,432,794 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. L16L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GARS1
NM_002047.4 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:4

Conservation

PhyloP100: 2.30

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:

GARS1-DT (HGNC:48951): (GARS1 divergent transcript)

GARS1-DT links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_002047.4

BP6

Variant 7-30594966-TCTG-T is Benign according to our data. Variant chr7-30594966-TCTG-T is described in ClinVar as [Benign]. Clinvar id is 416092.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr7-30594966-TCTG-T is described in Lovd as [Benign]. Variant chr7-30594966-TCTG-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00019 (272/1432794) while in subpopulation AMR AF= 0.00073 (32/43846). AF 95% confidence interval is 0.000531. There are 0 homozygotes in gnomad4_exome. There are 161 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 272 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GARS1	NM_002047.4 linkuse as main transcript	c.59_61del	p.Leu20del	inframe_deletion	1/17	ENST00000389266.8
GARS1	NM_001316772.1 linkuse as main transcript	c.-104_-102del		5_prime_UTR_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GARS1	ENST00000389266.8 linkuse as main transcript	c.59_61del	p.Leu20del	inframe_deletion	1/17	1	NM_002047.4	P2	P41250-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151984

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000190

AC:

272

AN:

1432794

Hom.:

AF XY:

0.000226

AC XY:

161

AN XY:

713094

show subpopulations

Gnomad4 AFR exome

AF:

0.000121

Gnomad4 AMR exome

AF:

0.000730

Gnomad4 ASJ exome

AF:

0.000426

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.000484

Gnomad4 FIN exome

AF:

0.000688

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.000201

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

151984

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74248

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00274

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Clinical Genetics, Academic Medical Center

- -

GARS1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 16, 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). -

Charcot-Marie-Tooth disease type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 15, 2023

- -

not provided

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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