rs863223328

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_002047.4(GARS1):c.95T>C(p.Leu32Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000701 in 1,426,720 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L32V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

GARS1
NM_002047.4 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.851

Publications

2 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 links:

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

GARS1-DT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.057976395).

BP6

Variant 7-30595016-T-C is Benign according to our data. Variant chr7-30595016-T-C is described in ClinVar as Benign. ClinVar VariationId is 217861.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.95T>C	p.Leu32Pro	missense_variant	Exon 1 of 17	ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 link	c.-68T>C		5_prime_UTR_variant	Exon 1 of 17		NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266.8 link	c.95T>C	p.Leu32Pro	missense_variant	Exon 1 of 17	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 link	c.95T>C	p.Leu32Pro	missense_variant	Exon 1 of 17			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 link	c.95T>C	p.Leu32Pro	missense_variant	Exon 1 of 16			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000444666.6 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 18	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 15			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 17			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 link	n.95T>C		non_coding_transcript_exon_variant	Exon 1 of 16			ENSP00000502681.1	A0A6Q8PHI7
GARS1	ENST00000675693.1 link	c.18+77T>C		intron_variant	Intron 1 of 17			ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000675051.1 link	c.22-3780T>C		intron_variant	Intron 1 of 16			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674815.1 link	c.-148+64T>C		intron_variant	Intron 1 of 16			ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 link	c.-184+64T>C		intron_variant	Intron 1 of 17			ENSP00000502451.1	A0A6Q8PGW4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000520

AC:

AN:

192172

AF XY:

0.00

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:

0.0000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000701

AC:

AN:

1426720

Hom.:

Cov.:

AF XY:

0.00000565

AC XY:

AN XY:

708488

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32996

American (AMR)

AF:

0.00

AC:

AN:

42292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25678

East Asian (EAS)

AF:

0.00

AC:

AN:

38486

South Asian (SAS)

AF:

0.00

AC:

AN:

82894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37124

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5492

European-Non Finnish (NFE)

AF:

0.00000907

AC:

AN:

1102408

Other (OTH)

AF:

0.00

AC:

AN:

59350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

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: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease

Benign:1

Oct 01, 2014

Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:research

Present in only four out of five affected family members, seen in one unaffected family member. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.9

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.064

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0017

LIST_S2

Benign

0.37

T;T

M_CAP

Uncertain

0.17

MetaRNN

Benign

0.058

T;T

MetaSVM

Benign

-0.90

PhyloP100

-0.85

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.36

N;.

REVEL

Benign

0.096

Sift

Benign

0.28

T;.

Sift4G

Benign

0.074

T;T

Polyphen

0.0

B;.

Vest4

0.067

MutPred

0.30

Gain of loop (P = 0.0013);Gain of loop (P = 0.0013);

MVP

0.093

MPC

0.56

ClinPred

0.066

GERP RS

-0.31

PromoterAI

-0.0090

Neutral

(source)

Varity_R

0.059

gMVP

0.30

Mutation Taster

=99/1

polymorphism

(source)

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