GeneBe

17-36601827-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024864.5(MRM1):​c.17C>T​(p.Thr6Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000331 in 1,572,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

MRM1
NM_024864.5 missense

Scores

1
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.415

Publications

1 publications found
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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.067323744).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MRM1NM_024864.5 linkc.17C>T p.Thr6Ile 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.17C>T p.Thr6Ile missense_variant Exon 1 of 5 1 NM_024864.5 ENSP00000481559.1 Q6IN84-1
MRM1ENST00000612760.1 linkc.-393C>T upstream_gene_variant 1 ENSP00000482526.1 A0A087WZC1

Frequencies

GnomAD3 genomes
AF:
0.0000526
AC:
8
AN:
152180
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000478
GnomAD2 exomes
AF:
0.0000226
AC:
5
AN:
221580
AF XY:
0.0000250
show subpopulations
Gnomad AFR exome
AF:
0.0000638
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:
0.0000291
Gnomad OTH exome
AF:
0.000184
GnomAD4 exome
AF:
0.0000310
AC:
44
AN:
1419944
Hom.:
0
Cov.:
31
AF XY:
0.0000228
AC XY:
16
AN XY:
701972
show subpopulations
African (AFR)
AF:
0.0000609
AC:
2
AN:
32864
American (AMR)
AF:
0.0000237
AC:
1
AN:
42204
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
23792
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39234
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81098
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
43538
Middle Eastern (MID)
AF:
0.000181
AC:
1
AN:
5510
European-Non Finnish (NFE)
AF:
0.0000320
AC:
35
AN:
1092966
Other (OTH)
AF:
0.0000851
AC:
5
AN:
58738
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.486
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
4
8
12
16
20
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000525
AC:
8
AN:
152298
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74466
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41576
American (AMR)
AF:
0.000261
AC:
4
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5168
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.0000294
AC:
2
AN:
68008
Other (OTH)
AF:
0.000473
AC:
1
AN:
2116
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.488
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000495
Hom.:
0
Bravo
AF:
0.0000831
ExAC
AF:
0.00000825
AC:
1

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jul 06, 2021
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.17C>T (p.T6I) 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 17, causing the threonine (T) at amino acid position 6 to be replaced by an isoleucine (I). 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
0.13
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
9.6
DANN
Benign
0.79
DEOGEN2
Benign
0.0093
T
Eigen
Benign
-0.84
Eigen_PC
Benign
-0.86
FATHMM_MKL
Benign
0.11
N
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.067
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
PhyloP100
0.41
PrimateAI
Uncertain
0.63
T
Sift4G
Benign
0.30
T
Polyphen
0.035
B
Vest4
0.20
MutPred
0.30
Loss of disorder (P = 0.0402);
MVP
0.16
ClinPred
0.040
T
GERP RS
2.8
PromoterAI
0.091
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.033
gMVP
0.65
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs200927938; hg19: chr17-34958256; API