7-30616026-C-A

Position:

• chr7-30616026-C-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The ENST00000389266.8(GARS1):​c.1162C>A​(p.Arg388Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000657 in 152,120 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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: GARS1 ENST00000389266.8 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.97

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 (HGNC:):

ACMG classification

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=-0.25).
• BP6: Variant 7-30616026-C-A is Benign according to our data. Variant chr7-30616026-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1082265.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GARS1	NM_002047.4	c.1162C>A	p.Arg388Arg	synonymous_variant	9/17	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.1000C>A	p.Arg334Arg	synonymous_variant	9/17		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.1162C>A	p.Arg388Arg	synonymous_variant	9/17	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.1162C>A	p.Arg388Arg	synonymous_variant	9/17			ENSP00000502513.1
GARS1	ENST00000675810.1	c.1060C>A	p.Arg354Arg	synonymous_variant	8/16			ENSP00000502743.1
GARS1	ENST00000675693.1	c.994C>A	p.Arg332Arg	synonymous_variant	10/18			ENSP00000502174.1
GARS1	ENST00000675051.1	c.961C>A	p.Arg321Arg	synonymous_variant	9/17			ENSP00000502296.1
GARS1	ENST00000674815.1	c.793C>A	p.Arg265Arg	synonymous_variant	9/17			ENSP00000502799.1
GARS1	ENST00000674851.1	c.793C>A	p.Arg265Arg	synonymous_variant	10/18			ENSP00000502451.1
GARS1	ENST00000444666.6	n.1162C>A		non_coding_transcript_exon_variant	9/18	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*876C>A		non_coding_transcript_exon_variant	10/18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*262C>A		non_coding_transcript_exon_variant	10/17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*500C>A		non_coding_transcript_exon_variant	10/18			ENSP00000502464.1
GARS1	ENST00000674807.1	n.1162C>A		non_coding_transcript_exon_variant	9/16			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*1032C>A		non_coding_transcript_exon_variant	10/18			ENSP00000501655.1
GARS1	ENST00000675859.1	n.1162C>A		non_coding_transcript_exon_variant	9/15			ENSP00000502033.1
GARS1	ENST00000676088.1	n.*1104C>A		non_coding_transcript_exon_variant	11/19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*107C>A		non_coding_transcript_exon_variant	9/17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*613C>A		non_coding_transcript_exon_variant	9/17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*451C>A		non_coding_transcript_exon_variant	10/18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*594C>A		non_coding_transcript_exon_variant	9/17			ENSP00000501980.1
GARS1	ENST00000676403.1	n.1162C>A		non_coding_transcript_exon_variant	9/16			ENSP00000502681.1
GARS1	ENST00000674616.1	n.*876C>A		3_prime_UTR_variant	10/18			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*262C>A		3_prime_UTR_variant	10/17			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*500C>A		3_prime_UTR_variant	10/18			ENSP00000502464.1
GARS1	ENST00000675529.1	n.*1032C>A		3_prime_UTR_variant	10/18			ENSP00000501655.1
GARS1	ENST00000676088.1	n.*1104C>A		3_prime_UTR_variant	11/19			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*107C>A		3_prime_UTR_variant	9/17			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*613C>A		3_prime_UTR_variant	9/17			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*451C>A		3_prime_UTR_variant	10/18			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*594C>A		3_prime_UTR_variant	9/17			ENSP00000501980.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

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.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74318

Gnomad4 AFR AF: 0.0000241

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: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Mar 25, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	9.9
DANN	Benign	0.65
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

Other links and lift over

dbSNP: rs759277467; hg19: chr7-30655642;