7-30609704-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_002047.4(GARS1):​c.855C>T​(p.Phe285Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000274 in 1,461,344 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: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GARS1
NM_002047.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.09
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]

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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=-0.2).
BP6
Variant 7-30609704-C-T is Benign according to our data. Variant chr7-30609704-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 758871.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GARS1NM_002047.4 linkc.855C>T p.Phe285Phe synonymous_variant Exon 7 of 17 ENST00000389266.8 NP_002038.2 P41250-1
GARS1NM_001316772.1 linkc.693C>T p.Phe231Phe synonymous_variant Exon 7 of 17 NP_001303701.1 P41250-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GARS1ENST00000389266.8 linkc.855C>T p.Phe285Phe synonymous_variant Exon 7 of 17 1 NM_002047.4 ENSP00000373918.3 P41250-1
GARS1ENST00000675651.1 linkc.855C>T p.Phe285Phe synonymous_variant Exon 7 of 17 ENSP00000502513.1 A0A6Q8PGZ8
GARS1ENST00000675810.1 linkc.753C>T p.Phe251Phe synonymous_variant Exon 6 of 16 ENSP00000502743.1 A0A6Q8PHH9
GARS1ENST00000675693.1 linkc.687C>T p.Phe229Phe synonymous_variant Exon 8 of 18 ENSP00000502174.1 A0A6Q8PGA8
GARS1ENST00000675051.1 linkc.654C>T p.Phe218Phe synonymous_variant Exon 7 of 17 ENSP00000502296.1 A0A6Q8PGI6
GARS1ENST00000674815.1 linkc.486C>T p.Phe162Phe synonymous_variant Exon 7 of 17 ENSP00000502799.1 A0A6Q8PGW4
GARS1ENST00000674851.1 linkc.486C>T p.Phe162Phe synonymous_variant Exon 8 of 18 ENSP00000502451.1 A0A6Q8PGW4
GARS1ENST00000444666.6 linkn.855C>T non_coding_transcript_exon_variant Exon 7 of 18 3 ENSP00000415447.2 H7C443
GARS1ENST00000674616.1 linkn.*569C>T non_coding_transcript_exon_variant Exon 8 of 18 ENSP00000502408.1 A0A6Q8PGT3
GARS1ENST00000674643.1 linkn.855C>T non_coding_transcript_exon_variant Exon 7 of 17 ENSP00000501636.1 A0A6Q8PF45
GARS1ENST00000674737.1 linkn.*193C>T non_coding_transcript_exon_variant Exon 8 of 18 ENSP00000502464.1 A0A6Q8PGZ9
GARS1ENST00000674807.1 linkn.855C>T non_coding_transcript_exon_variant Exon 7 of 16 ENSP00000502814.1 A0A6Q8PFZ6
GARS1ENST00000675529.1 linkn.*725C>T non_coding_transcript_exon_variant Exon 8 of 18 ENSP00000501655.1 A0A6Q8PFN0
GARS1ENST00000675859.1 linkn.855C>T non_coding_transcript_exon_variant Exon 7 of 15 ENSP00000502033.1 A0A6Q8PFZ6
GARS1ENST00000676088.1 linkn.*797C>T non_coding_transcript_exon_variant Exon 9 of 19 ENSP00000501884.1 A0A6Q8PFN0
GARS1ENST00000676140.1 linkn.855C>T non_coding_transcript_exon_variant Exon 7 of 17 ENSP00000502571.1 A0A6Q8PH49
GARS1ENST00000676164.1 linkn.*306C>T non_coding_transcript_exon_variant Exon 7 of 17 ENSP00000501986.1 A0A6Q8PFV5
GARS1ENST00000676210.1 linkn.*144C>T non_coding_transcript_exon_variant Exon 8 of 18 ENSP00000502373.1 A0A6Q8PGN7
GARS1ENST00000676259.1 linkn.*287C>T non_coding_transcript_exon_variant Exon 7 of 17 ENSP00000501980.1 A0A6Q8PFU7
GARS1ENST00000676403.1 linkn.855C>T non_coding_transcript_exon_variant Exon 7 of 16 ENSP00000502681.1 A0A6Q8PHI7
GARS1ENST00000674616.1 linkn.*569C>T 3_prime_UTR_variant Exon 8 of 18 ENSP00000502408.1 A0A6Q8PGT3
GARS1ENST00000674737.1 linkn.*193C>T 3_prime_UTR_variant Exon 8 of 18 ENSP00000502464.1 A0A6Q8PGZ9
GARS1ENST00000675529.1 linkn.*725C>T 3_prime_UTR_variant Exon 8 of 18 ENSP00000501655.1 A0A6Q8PFN0
GARS1ENST00000676088.1 linkn.*797C>T 3_prime_UTR_variant Exon 9 of 19 ENSP00000501884.1 A0A6Q8PFN0
GARS1ENST00000676164.1 linkn.*306C>T 3_prime_UTR_variant Exon 7 of 17 ENSP00000501986.1 A0A6Q8PFV5
GARS1ENST00000676210.1 linkn.*144C>T 3_prime_UTR_variant Exon 8 of 18 ENSP00000502373.1 A0A6Q8PGN7
GARS1ENST00000676259.1 linkn.*287C>T 3_prime_UTR_variant Exon 7 of 17 ENSP00000501980.1 A0A6Q8PFU7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461344
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
726986
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:
0.00000360
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease type 2 Benign:1
May 11, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.20
CADD
Benign
12
DANN
Benign
0.80
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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs786204099; hg19: chr7-30649320; API