Variant 7-30633785-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002047.4(GARS1):c.2145A>C(p.Thr715Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,608,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T715T) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GARS1
NM_002047.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.72

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 (HGNC:):

GARS1 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARS1	NM_002047.4 linkuse as main transcript	c.2145A>C	p.Thr715Thr	synonymous_variant	17/17	ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 linkuse as main transcript	c.1983A>C	p.Thr661Thr	synonymous_variant	17/17		NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266.8 linkuse as main transcript	c.2145A>C	p.Thr715Thr	synonymous_variant	17/17	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 linkuse as main transcript	c.2163A>C	p.Thr721Thr	synonymous_variant	17/17			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 linkuse as main transcript	c.2043A>C	p.Thr681Thr	synonymous_variant	16/16			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693.1 linkuse as main transcript	c.1977A>C	p.Thr659Thr	synonymous_variant	18/18			ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000675051.1 linkuse as main transcript	c.1944A>C	p.Thr648Thr	synonymous_variant	17/17			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674815.1 linkuse as main transcript	c.1776A>C	p.Thr592Thr	synonymous_variant	17/17			ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 linkuse as main transcript	c.1776A>C	p.Thr592Thr	synonymous_variant	18/18			ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 linkuse as main transcript	n.*566A>C		non_coding_transcript_exon_variant	18/18	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 linkuse as main transcript	n.*1859A>C		non_coding_transcript_exon_variant	18/18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 linkuse as main transcript	n.*1950A>C		non_coding_transcript_exon_variant	17/17			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 linkuse as main transcript	n.*1483A>C		non_coding_transcript_exon_variant	18/18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 linkuse as main transcript	n.*418A>C		non_coding_transcript_exon_variant	16/16			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 linkuse as main transcript	n.*2015A>C		non_coding_transcript_exon_variant	18/18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 linkuse as main transcript	n.*324A>C		non_coding_transcript_exon_variant	15/15			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 linkuse as main transcript	n.*2087A>C		non_coding_transcript_exon_variant	19/19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 linkuse as main transcript	n.*1090A>C		non_coding_transcript_exon_variant	17/17			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 linkuse as main transcript	n.*1596A>C		non_coding_transcript_exon_variant	17/17			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 linkuse as main transcript	n.*1434A>C		non_coding_transcript_exon_variant	18/18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 linkuse as main transcript	n.*1577A>C		non_coding_transcript_exon_variant	17/17			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 linkuse as main transcript	n.*230A>C		non_coding_transcript_exon_variant	16/16			ENSP00000502681.1	A0A6Q8PHI7
GARS1	ENST00000444666.6 linkuse as main transcript	n.*566A>C		3_prime_UTR_variant	18/18	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 linkuse as main transcript	n.*1859A>C		3_prime_UTR_variant	18/18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 linkuse as main transcript	n.*1950A>C		3_prime_UTR_variant	17/17			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 linkuse as main transcript	n.*1483A>C		3_prime_UTR_variant	18/18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 linkuse as main transcript	n.*418A>C		3_prime_UTR_variant	16/16			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 linkuse as main transcript	n.*2015A>C		3_prime_UTR_variant	18/18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 linkuse as main transcript	n.*324A>C		3_prime_UTR_variant	15/15			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 linkuse as main transcript	n.*2087A>C		3_prime_UTR_variant	19/19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 linkuse as main transcript	n.*1090A>C		3_prime_UTR_variant	17/17			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 linkuse as main transcript	n.*1596A>C		3_prime_UTR_variant	17/17			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 linkuse as main transcript	n.*1434A>C		3_prime_UTR_variant	18/18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 linkuse as main transcript	n.*1577A>C		3_prime_UTR_variant	17/17			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 linkuse as main transcript	n.*230A>C		3_prime_UTR_variant	16/16			ENSP00000502681.1	A0A6Q8PHI7

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151860

Hom.:

Cov.:

show subpopulations

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249520

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135374

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724756

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151860

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74172

show subpopulations

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:

0.0000294

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.38

DANN

Benign

0.69

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over