Genetic Variant MRM1:p.Gln145His (chr17-36602245-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024864.5(MRM1):c.435G>C(p.Gln145His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,456,796 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: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

MRM1
NM_024864.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.457

Publications

0 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]

MRM1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16480857).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRM1	NM_024864.5 link	c.435G>C	p.Gln145His	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
MRM1	ENST00000614766.5 link	c.435G>C	p.Gln145His	missense_variant	Exon 1 of 5	1	NM_024864.5	ENSP00000481559.1		Q6IN84-1
MRM1	ENST00000612760.1 link	c.-44+69G>C		intron_variant	Intron 1 of 4	1		ENSP00000482526.1		A0A087WZC1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000416

AC:

AN:

240228

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1456796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723944

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33408

American (AMR)

AF:

0.00

AC:

AN:

44586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26086

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39568

South Asian (SAS)

AF:

0.00

AC:

AN:

86118

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52072

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5736

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109122

Other (OTH)

AF:

0.00

AC:

AN:

60100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000832

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 02, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.435G>C (p.Q145H) alteration is located in exon 1 (coding exon 1) of the MRM1 gene. This alteration results from a G to C substitution at nucleotide position 435, causing the glutamine (Q) at amino acid position 145 to be replaced by a histidine (H). 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

0.17

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.033

Eigen

Benign

-0.031

Eigen_PC

Benign

-0.086

FATHMM_MKL

Benign

0.37

M_CAP

Benign

0.026

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

PhyloP100

0.46

PrimateAI

Benign

0.47

Sift4G

Benign

0.16

Polyphen

0.73

Vest4

0.32

MutPred

0.49

Gain of sheet (P = 0.1208);

MVP

0.57

ClinPred

0.76

GERP RS

1.6

PromoterAI

-0.017

Neutral

(source)

Varity_R

0.13

gMVP

0.54

Mutation Taster

=100/0

polymorphism

(source)

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

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chr17-36602245-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over