Genetic Variant NM_002047.4:c.1719T>C (chr7-30628579-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_002047.4(GARS1):c.1719T>C(p.Asn573Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,611,534 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)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GARS1
NM_002047.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.569

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 7-30628579-T-C is Benign according to our data. Variant chr7-30628579-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2052792.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.569 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4 link	c.1719T>C	p.Asn573Asn	synonymous_variant	Exon 14 of 17	ENST00000389266.8	NP_002038.2	P41250-1
GARS1	NM_001316772.1 link	c.1557T>C	p.Asn519Asn	synonymous_variant	Exon 14 of 17		NP_001303701.1	P41250-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GARS1	ENST00000389266.8 link	c.1719T>C	p.Asn573Asn	synonymous_variant	Exon 14 of 17	1	NM_002047.4	ENSP00000373918.3	P41250-1
GARS1	ENST00000675651.1 link	c.1719T>C	p.Asn573Asn	synonymous_variant	Exon 14 of 17			ENSP00000502513.1	A0A6Q8PGZ8
GARS1	ENST00000675810.1 link	c.1617T>C	p.Asn539Asn	synonymous_variant	Exon 13 of 16			ENSP00000502743.1	A0A6Q8PHH9
GARS1	ENST00000675693.1 link	c.1551T>C	p.Asn517Asn	synonymous_variant	Exon 15 of 18			ENSP00000502174.1	A0A6Q8PGA8
GARS1	ENST00000675051.1 link	c.1518T>C	p.Asn506Asn	synonymous_variant	Exon 14 of 17			ENSP00000502296.1	A0A6Q8PGI6
GARS1	ENST00000674815.1 link	c.1350T>C	p.Asn450Asn	synonymous_variant	Exon 14 of 17			ENSP00000502799.1	A0A6Q8PGW4
GARS1	ENST00000674851.1 link	c.1350T>C	p.Asn450Asn	synonymous_variant	Exon 15 of 18			ENSP00000502451.1	A0A6Q8PGW4
GARS1	ENST00000444666.6 link	n.*140T>C		non_coding_transcript_exon_variant	Exon 15 of 18	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 link	n.*1433T>C		non_coding_transcript_exon_variant	Exon 15 of 18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.*819T>C		non_coding_transcript_exon_variant	Exon 15 of 17			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.*1057T>C		non_coding_transcript_exon_variant	Exon 15 of 18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000674807.1 link	n.1633T>C		non_coding_transcript_exon_variant	Exon 13 of 16			ENSP00000502814.1	A0A6Q8PFZ6
GARS1	ENST00000675529.1 link	n.*1589T>C		non_coding_transcript_exon_variant	Exon 15 of 18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000675859.1 link	n.1633T>C		non_coding_transcript_exon_variant	Exon 13 of 15			ENSP00000502033.1	A0A6Q8PFZ6
GARS1	ENST00000676088.1 link	n.*1661T>C		non_coding_transcript_exon_variant	Exon 16 of 19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.*664T>C		non_coding_transcript_exon_variant	Exon 14 of 17			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 link	n.*1170T>C		non_coding_transcript_exon_variant	Exon 14 of 17			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 link	n.*1008T>C		non_coding_transcript_exon_variant	Exon 15 of 18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.*1151T>C		non_coding_transcript_exon_variant	Exon 14 of 17			ENSP00000501980.1	A0A6Q8PFU7
GARS1	ENST00000676403.1 link	n.1719T>C		non_coding_transcript_exon_variant	Exon 14 of 16			ENSP00000502681.1	A0A6Q8PHI7
GARS1	ENST00000444666.6 link	n.*140T>C		3_prime_UTR_variant	Exon 15 of 18	3		ENSP00000415447.2	H7C443
GARS1	ENST00000674616.1 link	n.*1433T>C		3_prime_UTR_variant	Exon 15 of 18			ENSP00000502408.1	A0A6Q8PGT3
GARS1	ENST00000674643.1 link	n.*819T>C		3_prime_UTR_variant	Exon 15 of 17			ENSP00000501636.1	A0A6Q8PF45
GARS1	ENST00000674737.1 link	n.*1057T>C		3_prime_UTR_variant	Exon 15 of 18			ENSP00000502464.1	A0A6Q8PGZ9
GARS1	ENST00000675529.1 link	n.*1589T>C		3_prime_UTR_variant	Exon 15 of 18			ENSP00000501655.1	A0A6Q8PFN0
GARS1	ENST00000676088.1 link	n.*1661T>C		3_prime_UTR_variant	Exon 16 of 19			ENSP00000501884.1	A0A6Q8PFN0
GARS1	ENST00000676140.1 link	n.*664T>C		3_prime_UTR_variant	Exon 14 of 17			ENSP00000502571.1	A0A6Q8PH49
GARS1	ENST00000676164.1 link	n.*1170T>C		3_prime_UTR_variant	Exon 14 of 17			ENSP00000501986.1	A0A6Q8PFV5
GARS1	ENST00000676210.1 link	n.*1008T>C		3_prime_UTR_variant	Exon 15 of 18			ENSP00000502373.1	A0A6Q8PGN7
GARS1	ENST00000676259.1 link	n.*1151T>C		3_prime_UTR_variant	Exon 14 of 17			ENSP00000501980.1	A0A6Q8PFU7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152250

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459284

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726058

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:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74388

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000193

Hom.:

Bravo

AF:

0.0000113

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

Dec 22, 2021

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

-0.46

CADD

Benign

8.0

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over