chr12-57488311-A-G

Variant names:

• chr12-57488311-A-G
• rs508904
• NM_004990.4:c.109+112A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.726
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -20 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 VariationId is 1257282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004990.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARS1	NM_004990.4	MANE Select	c.109+112A>G		intron	N/A	NP_004981.2
	ARHGAP9	NM_001319850.2		c.-204+301T>C		intron	N/A	NP_001306779.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARS1	ENST00000262027.10	TSL:1 MANE Select	c.109+112A>G		intron	N/A	ENSP00000262027.5
	ARHGAP9	ENST00000393797.7	TSL:1	c.-204+301T>C		intron	N/A	ENSP00000377386.3
	MARS1	ENST00000948582.1		c.109+112A>G		intron	N/A	ENSP00000618641.1

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

African (AFR) AF: 0.198 AC: 4091 AN: 20638

American (AMR) AF: 0.107 AC: 3053 AN: 28556

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 3128 AN: 17376

East Asian (EAS) AF: 0.210 AC: 7336 AN: 34876

South Asian (SAS) AF: 0.142 AC: 8725 AN: 61596

European-Finnish (FIN) AF: 0.208 AC: 7710 AN: 37090

Middle Eastern (MID) AF: 0.157 AC: 454 AN: 2894

European-Non Finnish (NFE) AF: 0.124 AC: 71485 AN: 577006

Other (OTH) AF: 0.146 AC: 5628 AN: 38622

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

African (AFR) AF: 0.198 AC: 8204 AN: 41462

American (AMR) AF: 0.141 AC: 2152 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 631 AN: 3466

East Asian (EAS) AF: 0.262 AC: 1350 AN: 5154

South Asian (SAS) AF: 0.152 AC: 735 AN: 4824

European-Finnish (FIN) AF: 0.207 AC: 2185 AN: 10566

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8682 AN: 67954

Other (OTH) AF: 0.143 AC: 302 AN: 2110

Alfa AF: 0.132 Hom.: 2211

Bravo AF: 0.158

Asia WGS AF: 0.173 AC: 603 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.53
DANN	Benign	0.54
PhyloP100		-0.73
PromoterAI		0.066	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs508904; hg19: chr12-57882094;