17-36602006-C-T

Variant names:

• chr17-36602006-C-T
• rs150793618
• ENST00000612760.1:c.-214C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000612760.1(MRM1):​c.-214C>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MRM1 ENST00000612760.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.976
• Publications: 2 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40767506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRM1	NM_024864.5	c.196C>T	p.Arg66Cys	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	ENST00000612760.1	c.-214C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 5	1		ENSP00000482526.1
MRM1	ENST00000614766.5	c.196C>T	p.Arg66Cys	missense_variant	Exon 1 of 5	1	NM_024864.5	ENSP00000481559.1
MRM1	ENST00000612760.1	c.-214C>T		5_prime_UTR_variant	Exon 1 of 5	1		ENSP00000482526.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 247584 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.17
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Benign	0.67	D
M_CAP	Uncertain	0.24	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.45	T
MutationAssessor	Pathogenic	3.2	M
PhyloP100		0.98
PrimateAI	Pathogenic	0.86	D
Sift4G	Uncertain	0.0040	D
Polyphen		1.0	D
Vest4		0.20
MutPred		0.70		Loss of MoRF binding (P = 0.0214);
MVP		0.48
ClinPred		0.92	D
GERP RS		4.6
PromoterAI		-0.0014	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.50
gMVP		0.74

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: rs150793618; hg19: chr17-34958435;