dbSNP rs2240401: GARS1:c.2095-6C>G (chr7-30633729-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002047.4(GARS1):c.2095-6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 30)

Failed GnomAD Quality Control

Consequence

GARS1
NM_002047.4 splice_region, intron

Scores

Splicing: ADA: 0.00008648

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.97

Publications

18 publications found

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 Gene-Disease associations (from GenCC):

Charcot-Marie-Tooth disease type 2D
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet
neuronopathy, distal hereditary motor, type 5A
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, Laboratory for Molecular Medicine
spinal muscular atrophy, infantile, James type
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

GARS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.2095-6C>G		splice_region_variant, intron_variant	Intron 16 of 16	ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 link	c.1933-6C>G		splice_region_variant, intron_variant	Intron 16 of 16		NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266.8 link	c.2095-6C>G	splice_region_variant, intron_variant	Intron 16 of 16	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 link	c.2113-6C>G	splice_region_variant, intron_variant	Intron 16 of 16			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 link	c.1993-6C>G	splice_region_variant, intron_variant	Intron 15 of 15			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693.1 link	c.1927-6C>G	splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000675051.1 link	c.1894-6C>G	splice_region_variant, intron_variant	Intron 16 of 16			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674815.1 link	c.1726-6C>G	splice_region_variant, intron_variant	Intron 16 of 16			ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 link	c.1726-6C>G	splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 link	n.*516-6C>G	splice_region_variant, intron_variant	Intron 17 of 17	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 link	n.*1809-6C>G	splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.*1900-6C>G	splice_region_variant, intron_variant	Intron 16 of 16			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.*1433-6C>G	splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 link	n.*368-6C>G	splice_region_variant, intron_variant	Intron 15 of 15			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 link	n.*1965-6C>G	splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 link	n.*274-6C>G	splice_region_variant, intron_variant	Intron 14 of 14			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 link	n.*2037-6C>G	splice_region_variant, intron_variant	Intron 18 of 18			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.*1040-6C>G	splice_region_variant, intron_variant	Intron 16 of 16			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 link	n.*1546-6C>G	splice_region_variant, intron_variant	Intron 16 of 16			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 link	n.*1384-6C>G	splice_region_variant, intron_variant	Intron 17 of 17			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.*1527-6C>G	splice_region_variant, intron_variant	Intron 16 of 16			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 link	n.*180-6C>G	splice_region_variant, intron_variant	Intron 15 of 15			ENSP00000502681.1	A0A6Q8PHI7

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151836

Hom.:

Cov.:

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

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74118

African (AFR)

AF:

0.00

AC:

AN:

41332

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67972

Other (OTH)

AF:

0.00

AC:

AN:

2086

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.18

(source)

DANN

Benign

0.52

PhyloP100

-2.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000086

dbscSNV1_RF

Benign

0.10

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over