dbSNP rs779554507: MRM1:p.Leu4Pro (chr17-36601821-T-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.11T>C(p.Leu4Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000777 in 1,415,148 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: 0.0000078 ( 0 hom. )

Consequence

MRM1
NM_024864.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.630

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=0.078005284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRM1	NM_024864.5 link	c.11T>C	p.Leu4Pro	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.11T>C	p.Leu4Pro	missense_variant	Exon 1 of 5	1	NM_024864.5	ENSP00000481559.1		Q6IN84-1
MRM1	ENST00000612760.1 link	c.-399T>C		upstream_gene_variant		1		ENSP00000482526.1		A0A087WZC1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000777

AC:

AN:

1415148

Hom.:

Cov.:

AF XY:

0.00000858

AC XY:

AN XY:

699052

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32792

American (AMR)

AF:

0.00

AC:

AN:

41886

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23394

East Asian (EAS)

AF:

0.00

AC:

AN:

39228

South Asian (SAS)

AF:

0.00

AC:

AN:

80088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42794

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5448

European-Non Finnish (NFE)

AF:

0.0000101

AC:

AN:

1090974

Other (OTH)

AF:

0.00

AC:

AN:

58544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 15, 2021

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.11T>C (p.L4P) alteration is located in exon 1 (coding exon 1) of the MRM1 gene. This alteration results from a T to C substitution at nucleotide position 11, causing the leucine (L) at amino acid position 4 to be replaced by a proline (P). 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

0.070

BayesDel_addAF

Benign

-0.053

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.011

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.12

M_CAP

Benign

0.012

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

0.63

PrimateAI

Uncertain

0.61

Sift4G

Benign

0.095

Polyphen

0.0050

Vest4

0.36

MutPred

0.48

Loss of stability (P = 0.0051);

MVP

0.27

ClinPred

0.079

GERP RS

0.68

PromoterAI

-0.043

Neutral

(source)

Varity_R

0.19

gMVP

0.65

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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rs779554507

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