7-30632320-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_002047.4(GARS1):c.1977C>T(p.Ala659Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 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 Likely benign (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GARS1
NM_002047.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.66

Publications

0 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: Benign. The variant received -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 7-30632320-C-T is Benign according to our data. Variant chr7-30632320-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 476754.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.65 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.1977C>T	p.Ala659Ala	synonymous_variant	Exon 16 of 17	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1 link	c.1815C>T	p.Ala605Ala	synonymous_variant	Exon 16 of 17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
GARS1	ENST00000389266.8 link	c.1977C>T	p.Ala659Ala	synonymous_variant	Exon 16 of 17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1 link	c.1995C>T	p.Ala665Ala	synonymous_variant	Exon 16 of 17			ENSP00000502513.1
GARS1	ENST00000675810.1 link	c.1875C>T	p.Ala625Ala	synonymous_variant	Exon 15 of 16			ENSP00000502743.1
GARS1	ENST00000675693.1 link	c.1809C>T	p.Ala603Ala	synonymous_variant	Exon 17 of 18			ENSP00000502174.1
GARS1	ENST00000675051.1 link	c.1776C>T	p.Ala592Ala	synonymous_variant	Exon 16 of 17			ENSP00000502296.1
GARS1	ENST00000674815.1 link	c.1608C>T	p.Ala536Ala	synonymous_variant	Exon 16 of 17			ENSP00000502799.1
GARS1	ENST00000674851.1 link	c.1608C>T	p.Ala536Ala	synonymous_variant	Exon 17 of 18			ENSP00000502451.1
GARS1	ENST00000444666.6 link	n.*398C>T		non_coding_transcript_exon_variant	Exon 17 of 18	3		ENSP00000415447.2
GARS1	ENST00000674616.1 link	n.*1691C>T		non_coding_transcript_exon_variant	Exon 17 of 18			ENSP00000502408.1
GARS1	ENST00000674643.1 link	n.*1782C>T		non_coding_transcript_exon_variant	Exon 16 of 17			ENSP00000501636.1
GARS1	ENST00000674737.1 link	n.*1315C>T		non_coding_transcript_exon_variant	Exon 17 of 18			ENSP00000502464.1
GARS1	ENST00000674807.1 link	n.*250C>T		non_coding_transcript_exon_variant	Exon 15 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1 link	n.*1847C>T		non_coding_transcript_exon_variant	Exon 17 of 18			ENSP00000501655.1
GARS1	ENST00000675859.1 link	n.*156C>T		non_coding_transcript_exon_variant	Exon 14 of 15			ENSP00000502033.1
GARS1	ENST00000676088.1 link	n.*1919C>T		non_coding_transcript_exon_variant	Exon 18 of 19			ENSP00000501884.1
GARS1	ENST00000676140.1 link	n.*922C>T		non_coding_transcript_exon_variant	Exon 16 of 17			ENSP00000502571.1
GARS1	ENST00000676164.1 link	n.*1428C>T		non_coding_transcript_exon_variant	Exon 16 of 17			ENSP00000501986.1
GARS1	ENST00000676210.1 link	n.*1266C>T		non_coding_transcript_exon_variant	Exon 17 of 18			ENSP00000502373.1
GARS1	ENST00000676259.1 link	n.*1409C>T		non_coding_transcript_exon_variant	Exon 16 of 17			ENSP00000501980.1
GARS1	ENST00000676403.1 link	n.*62C>T		non_coding_transcript_exon_variant	Exon 15 of 16			ENSP00000502681.1
GARS1	ENST00000444666.6 link	n.*398C>T		3_prime_UTR_variant	Exon 17 of 18	3		ENSP00000415447.2
GARS1	ENST00000674616.1 link	n.*1691C>T		3_prime_UTR_variant	Exon 17 of 18			ENSP00000502408.1
GARS1	ENST00000674643.1 link	n.*1782C>T		3_prime_UTR_variant	Exon 16 of 17			ENSP00000501636.1
GARS1	ENST00000674737.1 link	n.*1315C>T		3_prime_UTR_variant	Exon 17 of 18			ENSP00000502464.1
GARS1	ENST00000674807.1 link	n.*250C>T		3_prime_UTR_variant	Exon 15 of 16			ENSP00000502814.1
GARS1	ENST00000675529.1 link	n.*1847C>T		3_prime_UTR_variant	Exon 17 of 18			ENSP00000501655.1
GARS1	ENST00000675859.1 link	n.*156C>T		3_prime_UTR_variant	Exon 14 of 15			ENSP00000502033.1
GARS1	ENST00000676088.1 link	n.*1919C>T		3_prime_UTR_variant	Exon 18 of 19			ENSP00000501884.1
GARS1	ENST00000676140.1 link	n.*922C>T		3_prime_UTR_variant	Exon 16 of 17			ENSP00000502571.1
GARS1	ENST00000676164.1 link	n.*1428C>T		3_prime_UTR_variant	Exon 16 of 17			ENSP00000501986.1
GARS1	ENST00000676210.1 link	n.*1266C>T		3_prime_UTR_variant	Exon 17 of 18			ENSP00000502373.1
GARS1	ENST00000676259.1 link	n.*1409C>T		3_prime_UTR_variant	Exon 16 of 17			ENSP00000501980.1
GARS1	ENST00000676403.1 link	n.*62C>T		3_prime_UTR_variant	Exon 15 of 16			ENSP00000502681.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249536

AF XY:

0.00000739

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461882

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112002

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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. -

Charcot-Marie-Tooth disease type 2

Benign:1

May 01, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over