7-30633799-A-C
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2
The NM_002047.4(GARS1):āc.2159A>Cā(p.Glu720Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,608,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E720V) has been classified as Uncertain significance.
Frequency
Consequence
NM_002047.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GARS1 | NM_002047.4 | c.2159A>C | p.Glu720Ala | missense_variant | 17/17 | ENST00000389266.8 | |
GARS1 | NM_001316772.1 | c.1997A>C | p.Glu666Ala | missense_variant | 17/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GARS1 | ENST00000389266.8 | c.2159A>C | p.Glu720Ala | missense_variant | 17/17 | 1 | NM_002047.4 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 151800Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 249546Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135386
GnomAD4 exome AF: 0.00000618 AC: 9AN: 1456182Hom.: 0 Cov.: 42 AF XY: 0.00000414 AC XY: 3AN XY: 724468
GnomAD4 genome AF: 0.0000132 AC: 2AN: 151924Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74250
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 23, 2021 | The c.2159A>C (p.E720A) alteration is located in exon 17 (coding exon 17) of the GARS gene. This alteration results from a A to C substitution at nucleotide position 2159, causing the glutamic acid (E) at amino acid position 720 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 18, 2017 | - - |
Charcot-Marie-Tooth disease type 2D Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 19, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Charcot-Marie-Tooth disease type 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Mar 24, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at