Variant 6-24416432-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020662.4(MRS2):c.755A>G(p.Lys252Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000515 in 1,591,162 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

MRS2
NM_020662.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.89

Variant links:

Genes affected

MRS2 (HGNC:13785): (magnesium transporter MRS2) Enables magnesium ion transmembrane transporter activity. Involved in mitochondrial magnesium ion transmembrane transport. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

MRS2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRS2	NM_020662.4 linkuse as main transcript	c.755A>G	p.Lys252Arg	missense_variant	7/11	ENST00000378386.8	NP_065713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRS2	ENST00000378386.8 linkuse as main transcript	c.755A>G	p.Lys252Arg	missense_variant	7/11	1	NM_020662.4	ENSP00000367637	P1	Q9HD23-1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

249232

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

134982

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000590

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000972

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1438996

Hom.:

Cov.:

AF XY:

0.0000446

AC XY:

AN XY:

717456

show subpopulations

Gnomad4 AFR exome

AF:

0.0000304

Gnomad4 AMR exome

AF:

0.0000680

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.000937

Gnomad4 NFE exome

AF:

0.00000824

Gnomad4 OTH exome

AF:

0.0000671

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.000132

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Oct 04, 2022

The c.755A>G (p.K252R) alteration is located in exon 7 (coding exon 7) of the MRS2 gene. This alteration results from a A to G substitution at nucleotide position 755, causing the lysine (K) at amino acid position 252 to be replaced by an arginine (R). 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

-0.23

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.075

.;T;.;T

Eigen

Benign

0.12

Eigen_PC

Benign

0.17

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.86

D;D;D;D

M_CAP

Benign

0.022

MetaRNN

Benign

0.062

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.035

.;.;N;N

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

0.54

N;.;N;N

REVEL

Benign

0.26

Sift

Benign

0.82

T;.;T;T

Sift4G

Benign

0.17

T;D;T;T

Polyphen

1.0, 0.99

.;.;D;D

Vest4

0.42

MVP

0.44

MPC

0.99

ClinPred

0.14

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.068

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.34

Position offset: 1

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