Variant chr17-791665-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000304478.9(MRM3):c.859G>T(p.Ala287Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000449 in 1,614,106 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts 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: 0.00047 ( 1 hom. )

Consequence

MRM3
ENST00000304478.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.97

Variant links:

Genes affected

MRM3 (HGNC:18485): (mitochondrial rRNA methyltransferase 3) Efficient translation of mitochondrial-derived transcripts requires proper assembly of the large subunit of the mitochondrial ribosome. Central to the biogenesis of this large subunit is the A-loop of mitochondrial 16S rRNA, which is modified by three rRNA methyltransferases located near mtDNA nucleoids. The protein encoded by this gene methylates G(1370) of 16S rRNA, and this modification is necessary for proper ribosomal large subnit assembly. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

MRM3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29964542).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRM3	NM_018146.4 linkuse as main transcript	c.859G>T	p.Ala287Ser	missense_variant	4/4	ENST00000304478.9	NP_060616.1	Q9HC36
MRM3	NM_001317947.2 linkuse as main transcript	c.271G>T	p.Ala91Ser	missense_variant	3/3		NP_001304876.1	Q9HC36

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MRM3	ENST00000304478.9 linkuse as main transcript	c.859G>T	p.Ala287Ser	missense_variant	4/4	1	NM_018146.4	ENSP00000306080.4	Q9HC36
MRM3	ENST00000574509.1 linkuse as main transcript	n.*281G>T		non_coding_transcript_exon_variant	3/3	2		ENSP00000458328.1	I3L0T6
MRM3	ENST00000574509.1 linkuse as main transcript	n.*281G>T		3_prime_UTR_variant	3/3	2		ENSP00000458328.1	I3L0T6

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000338

AC:

AN:

251496

Hom.:

AF XY:

0.000427

AC XY:

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000483

Gnomad OTH exome

AF:

0.000814

GnomAD4 exome

AF:

0.000467

AC:

683

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000473

AC XY:

344

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.00180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000546

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000276

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000484

Hom.:

Bravo

AF:

0.000291

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000296

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.000533

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

Jun 21, 2021

The c.859G>T (p.A287S) alteration is located in exon 4 (coding exon 4) of the MRM3 gene. This alteration results from a G to T substitution at nucleotide position 859, causing the alanine (A) at amino acid position 287 to be replaced by a serine (S). 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

0.34

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.061

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

M_CAP

Benign

0.039

MetaRNN

Benign

0.30

MetaSVM

Benign

-0.61

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.4

REVEL

Uncertain

0.33

Sift

Uncertain

0.016

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.72

MVP

0.41

MPC

0.59

ClinPred

0.25

GERP RS

5.6

Varity_R

0.35

gMVP

0.64

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