17-36602063-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_024864.5(MRM1):​c.253C>T​(p.Arg85Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000162 in 1,609,518 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

MRM1
NM_024864.5 missense

Scores

2
7
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRM1NM_024864.5 linkc.253C>T p.Arg85Trp missense_variant Exon 1 of 5 ENST00000614766.5 NP_079140.2 Q6IN84-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MRM1ENST00000614766.5 linkc.253C>T p.Arg85Trp missense_variant Exon 1 of 5 1 NM_024864.5 ENSP00000481559.1 Q6IN84-1
MRM1ENST00000612760 linkc.-157C>T 5_prime_UTR_variant Exon 1 of 5 1 ENSP00000482526.1 A0A087WZC1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152182
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000821
AC:
2
AN:
243678
Hom.:
0
AF XY:
0.00000752
AC XY:
1
AN XY:
132950
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000181
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000158
AC:
23
AN:
1457336
Hom.:
0
Cov.:
31
AF XY:
0.0000152
AC XY:
11
AN XY:
724978
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152182
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000264
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 28, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.253C>T (p.R85W) alteration is located in exon 1 (coding exon 1) of the MRM1 gene. This alteration results from a C to T substitution at nucleotide position 253, causing the arginine (R) at amino acid position 85 to be replaced by a tryptophan (W). 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
0.15
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Uncertain
-0.040
CADD
Benign
21
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.047
T
Eigen
Uncertain
0.38
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Uncertain
0.81
D
M_CAP
Benign
0.042
D
MetaRNN
Uncertain
0.59
D
MetaSVM
Benign
-0.87
T
MutationAssessor
Benign
1.4
L
PrimateAI
Pathogenic
0.84
D
Sift4G
Uncertain
0.0090
D
Polyphen
1.0
D
Vest4
0.46
MutPred
0.73
Loss of disorder (P = 2e-04);
MVP
0.58
ClinPred
0.78
D
GERP RS
4.2
Varity_R
0.21
gMVP
0.81

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1213171072; hg19: chr17-34958492; API