Genetic Variant NM_013393.3:c.32C>T (chr7-2239684-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_013393.3(MRM2):c.32C>T(p.Ser11Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00369 in 1,612,880 control chromosomes in the GnomAD database, including 181 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.019 ( 97 hom., cov: 31)

Exomes 𝑓: 0.0021 ( 84 hom. )

Consequence

MRM2
NM_013393.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.163

Publications

4 publications found

Variant links:

Genes affected

MRM2 (HGNC:16352): (mitochondrial rRNA methyltransferase 2) The protein encoded by this gene is a member of the S-adenosylmethionine-binding protein family. It is a nucleolar protein and it may be involved in the processing and modification of rRNA. This gene has been suggested to be involved in cell cycle control and DNA repair. [provided by RefSeq, Jul 2008]

MRM2 Gene-Disease associations (from GenCC):

mitochondrial DNA depletion syndrome 17
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

MRM2 links:

ENSG00000286192 (HGNC:):

ENSG00000286192 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 7-2239684-G-A is Benign according to our data. Variant chr7-2239684-G-A is described in ClinVar as Benign. ClinVar VariationId is 776192.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013393.3. 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
	MRM2	NM_013393.3	MANE Select	c.32C>T	p.Ser11Phe	missense	Exon 2 of 3	NP_037525.1	Q9UI43

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MRM2	ENST00000242257.14	TSL:1 MANE Select	c.32C>T	p.Ser11Phe	missense	Exon 2 of 3	ENSP00000242257.8	Q9UI43
MRM2	ENST00000486040.1	TSL:1	n.32C>T		non_coding_transcript_exon	Exon 2 of 4	ENSP00000498090.1	A0A3B3ITW8
ENSG00000286192	ENST00000651235.1		n.32C>T		non_coding_transcript_exon	Exon 2 of 24	ENSP00000498895.1	A0A3B3ITW8

Frequencies

GnomAD3 genomes

AF:

0.0186

AC:

2830

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0648

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00569

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0134

GnomAD2 exomes

AF:

0.00489

AC:

1227

AN:

250882

AF XY:

0.00357

show subpopulations

Gnomad AFR exome

AF:

0.0664

Gnomad AMR exome

AF:

0.00307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000265

Gnomad OTH exome

AF:

0.00180

GnomAD4 exome

AF:

0.00213

AC:

3114

AN:

1460622

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

1344

AN XY:

726346

show subpopulations

African (AFR)

AF:

0.0701

AC:

2347

AN:

33462

American (AMR)

AF:

0.00351

AC:

157

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.000139

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53210

Middle Eastern (MID)

AF:

0.00538

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000258

AC:

287

AN:

1111092

Other (OTH)

AF:

0.00464

AC:

280

AN:

60338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

154

308

461

615

769

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

234

312

390

<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:

0.0187

AC:

2842

AN:

152258

Hom.:

Cov.:

AF XY:

0.0178

AC XY:

1328

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0649

AC:

2694

AN:

41540

American (AMR)

AF:

0.00569

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000623

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000397

AC:

AN:

68024

Other (OTH)

AF:

0.0133

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

135

270

406

541

676

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0147

Hom.:

Bravo

AF:

0.0217

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0570

AC:

251

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00609

AC:

740

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

MRM2-related disorder (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.69

DEOGEN2

Benign

0.087

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

PhyloP100

0.16

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.69

REVEL

Benign

0.10

Sift

Benign

0.73

Sift4G

Benign

0.73

Polyphen

0.0030

Vest4

0.24

MVP

0.37

MPC

0.20

ClinPred

0.0029

GERP RS

0.86

Varity_R

0.077

gMVP

0.35

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.21

Position offset: 23

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over