17-36602208-A-G

Variant names:

• chr17-36602208-A-G
• NM_024864.5:c.398A>G

Variant summary

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

The NM_024864.5(MRM1):​c.398A>G​(p.Glu133Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRM1 NM_024864.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.88
• Publications: 0 publications found

Genes affected

MRM1 (HGNC:26202): (mitochondrial rRNA methyltransferase 1) Enables rRNA (guanosine-2'-O-)-methyltransferase activity. Predicted to be involved in rRNA 2'-O-methylation. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

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=0.14108592).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRM1	NM_024864.5	c.398A>G	p.Glu133Gly	missense_variant	Exon 1 of 5	ENST00000614766.5	NP_079140.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRM1	ENST00000614766.5	c.398A>G	p.Glu133Gly	missense_variant	Exon 1 of 5	1	NM_024864.5	ENSP00000481559.1
MRM1	ENST00000612760.1	c.-44+32A>G		intron_variant	Intron 1 of 4	1		ENSP00000482526.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.398A>G (p.E133G) alteration is located in exon 1 (coding exon 1) of the MRM1 gene. This alteration results from a A to G substitution at nucleotide position 398, causing the glutamic acid (E) at amino acid position 133 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.071
FATHMM_MKL	Uncertain	0.79	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		4.9
PrimateAI	Benign	0.47	T
Sift4G	Benign	0.15	T
Polyphen		0.15	B
Vest4		0.21
MutPred		0.26		Loss of stability (P = 0.1087);
MVP		0.62
ClinPred		0.83	D
GERP RS		4.7
PromoterAI		-0.014	Neutral
Varity_R		0.072
gMVP		0.62

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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

hg19: chr17-34958637;