Variant chr17-36602037-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000614766.5(MRM1):c.227C>G(p.Ala76Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000268 in 1,610,156 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00027 ( 1 hom. )

Consequence

MRM1
ENST00000614766.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.397

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]

MRM1 links:

MRM1 (HGNC:):

MRM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.01545167).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRM1	NM_024864.5 linkuse as main transcript	c.227C>G	p.Ala76Gly	missense_variant	1/5	ENST00000614766.5	NP_079140.2	Q6IN84-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRM1	ENST00000614766.5 linkuse as main transcript	c.227C>G	p.Ala76Gly	missense_variant	1/5	1	NM_024864.5	ENSP00000481559.1		Q6IN84-1
MRM1	ENST00000612760.1 linkuse as main transcript	c.-183C>G		5_prime_UTR_variant	1/5	1		ENSP00000482526.1		A0A087WZC1

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000916

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000402

AC:

AN:

246220

Hom.:

AF XY:

0.000366

AC XY:

AN XY:

133936

show subpopulations

Gnomad AFR exome

AF:

0.000128

Gnomad AMR exome

AF:

0.000812

Gnomad ASJ exome

AF:

0.000600

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.000150

Gnomad NFE exome

AF:

0.000440

Gnomad OTH exome

AF:

0.00166

GnomAD4 exome

AF:

0.000267

AC:

389

AN:

1457832

Hom.:

Cov.:

AF XY:

0.000291

AC XY:

211

AN XY:

724986

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000828

Gnomad4 ASJ exome

AF:

0.000422

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.000234

Gnomad4 NFE exome

AF:

0.000247

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.000276

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.000915

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000474

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000468

AC:

ExAC

AF:

0.000437

AC:

EpiCase

AF:

0.00104

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2021

The c.227C>G (p.A76G) alteration is located in exon 1 (coding exon 1) of the MRM1 gene. This alteration results from a C to G substitution at nucleotide position 227, causing the alanine (A) at amino acid position 76 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

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.030

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.20

M_CAP

Benign

0.0074

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.76

Sift4G

Benign

0.37

Polyphen

0.32

Vest4

0.16

MVP

0.28

ClinPred

0.048

GERP RS

3.1

Varity_R

0.081

gMVP

0.56

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over