rs508904

Positions:

• chr12-57488311-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004990.4(MARS1):​c.109+112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.14 in 970,654 control chromosomes in the GnomAD database, including 10,389 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2114 hom., cov: 32)
  • Exomes 𝑓: 0.14 (8275 hom.)
• Consequence: MARS1 NM_004990.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.726

Genes affected

MARS1 (HGNC:6898): (methionyl-tRNA synthetase 1) This gene encodes a member of the class I family of aminoacyl-tRNA synthetases. These enzymes play a critical role in protein biosynthesis by charging tRNAs with their cognate amino acids. The encoded protein is a component of the multi-tRNA synthetase complex and catalyzes the ligation of methionine to tRNA molecules. [provided by RefSeq, Jan 2011]

ARHGAP9 (HGNC:14130): (Rho GTPase activating protein 9) This gene encodes a member of the Rho-GAP family of GTPase activating proteins. The protein has substantial GAP activity towards several Rho-family GTPases in vitro, converting them to an inactive GDP-bound state. It is implicated in regulating adhesion of hematopoietic cells to the extracellular matrix. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-57488311-A-G is Benign according to our data. Variant chr12-57488311-A-G is described in ClinVar as [Benign]. Clinvar id is 1257282.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MARS1	NM_004990.4	c.109+112A>G		intron_variant		ENST00000262027.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MARS1	ENST00000262027.10	c.109+112A>G		intron_variant		1	NM_004990.4	P1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24453 AN: 151882 Hom.: 2107 Cov.: 32

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.136 AC: 111610 AN: 818654 Hom.: 8275 Cov.: 11 AF XY: 0.136 AC XY: 56868 AN XY: 418492

Gnomad4 AFR exome AF: 0.198

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.210

Gnomad4 SAS exome AF: 0.142

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.124

Gnomad4 OTH exome AF: 0.146

GnomAD4 genome AF: 0.161 AC: 24487 AN: 152000 Hom.: 2114 Cov.: 32 AF XY: 0.168 AC XY: 12448 AN XY: 74280

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.182

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.128

Gnomad4 OTH AF: 0.143

Alfa AF: 0.133 Hom.: 1466

Bravo AF: 0.158

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.53
DANN	Benign	0.54
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs508904; hg19: chr12-57882094;