rs1166063337

Variant names:

• chr12-57488095-G-A
• rs1166063337
• NM_004990.4:c.5G>A

Your query was ambiguous. Multiple possible variants found:

• chr12-57488095-G-A
• chr12-57488095-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004990.4(MARS1):​c.5G>A​(p.Arg2Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MARS1 NM_004990.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11982691).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MARS1	NM_004990.4	c.5G>A	p.Arg2Lys	missense_variant	Exon 1 of 21	ENST00000262027.10	NP_004981.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MARS1	ENST00000262027.10	c.5G>A	p.Arg2Lys	missense_variant	Exon 1 of 21	1	NM_004990.4	ENSP00000262027.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	15
DANN	Benign	0.85
DEOGEN2	Benign	0.12	T;.;.;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.24	T;T;T;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.12	T;T;T;T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	-1.4	N;.;.;.
PhyloP100		1.3
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	0.14	N;.;.;.
REVEL	Uncertain	0.34
Sift	Benign	1.0	T;.;.;.
Sift4G	Benign	1.0	T;D;D;D
Polyphen		0.0010	B;.;.;.
Vest4		0.27
MutPred		0.39		Gain of catalytic residue at F4 (P = 0.0071);Gain of catalytic residue at F4 (P = 0.0071);Gain of catalytic residue at F4 (P = 0.0071);Gain of catalytic residue at F4 (P = 0.0071);
MVP		0.71
MPC		0.25
ClinPred		0.068	T
GERP RS		4.3
PromoterAI		0.14	Neutral
Varity_R		0.27
gMVP		0.48
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1166063337; hg19: chr12-57881878;