MARS1 p.Thr32Ser

Variant names:

• chr12-57488184-A-T
• NM_004990.4:c.94A>T
• MARS1 p.Thr32Ser

Your query was ambiguous. Multiple possible variants found:

• chr12-57488184-A-T
• chr12-57488185-C-G
• chr12-57488184-ACT-TCC
• chr12-57488184-ACT-TCA
• chr12-57488184-ACT-TCG
• chr12-57488185-CT-GC

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.94A>T​(p.Thr32Ser) 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. 16/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MARS1 NM_004990.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• 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=0.16194856).

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.94A>T	p.Thr32Ser	missense	Exon 1 of 21	NP_004981.2
	ARHGAP9	NM_001319850.2		c.-204+428T>A		intron	N/A	NP_001306779.2	Q9BRR9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MARS1	ENST00000262027.10	TSL:1 MANE Select	c.94A>T	p.Thr32Ser	missense	Exon 1 of 21	ENSP00000262027.5	P56192-1
	ARHGAP9	ENST00000393797.7	TSL:1	c.-204+428T>A		intron	N/A	ENSP00000377386.3	Q9BRR9-1
	MARS1	ENST00000948582.1		c.94A>T	p.Thr32Ser	missense	Exon 1 of 22	ENSP00000618641.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.073	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.4	L
PhyloP100		1.5
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.18
Sift	Benign	0.48	T
Sift4G	Benign	0.85	T
PromoterAI		0.0019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.34
gMVP		0.19
Mutation Taster		=275/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-57881967;