dbSNP rs3761788: MRS2:p.Gln236Gln (chr6-24415152-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020662.4(MRS2):c.708G>A(p.Gln236Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 1,588,986 control chromosomes in the GnomAD database, including 3,928 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.046 ( 219 hom., cov: 32)

Exomes 𝑓: 0.066 ( 3709 hom. )

Consequence

MRS2
NM_020662.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.388

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=0.388 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0703 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MRS2	NM_020662.4 link	c.708G>A	p.Gln236Gln	synonymous_variant	Exon 6 of 11	ENST00000378386.8	NP_065713.1	Q9HD23-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MRS2	ENST00000378386.8 link	c.708G>A	p.Gln236Gln	synonymous_variant	Exon 6 of 11	1	NM_020662.4	ENSP00000367637.3		Q9HD23-1

Frequencies

GnomAD3 genomes

AF:

0.0458

AC:

6968

AN:

152166

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0136

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0382

Gnomad ASJ

AF:

0.00806

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.00705

Gnomad FIN

AF:

0.0586

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0720

Gnomad OTH

AF:

0.0522

GnomAD2 exomes

AF:

0.0459

AC:

11447

AN:

249324

AF XY:

0.0451

show subpopulations

Gnomad AFR exome

AF:

0.0123

Gnomad AMR exome

AF:

0.0294

Gnomad ASJ exome

AF:

0.00847

Gnomad EAS exome

AF:

0.00273

Gnomad FIN exome

AF:

0.0575

Gnomad NFE exome

AF:

0.0735

Gnomad OTH exome

AF:

0.0446

GnomAD4 exome

AF:

0.0655

AC:

94137

AN:

1436704

Hom.:

3709

Cov.:

AF XY:

0.0638

AC XY:

45335

AN XY:

710952

show subpopulations

African (AFR)

AF:

0.00930

AC:

309

AN:

33220

American (AMR)

AF:

0.0306

AC:

1352

AN:

44170

Ashkenazi Jewish (ASJ)

AF:

0.00934

AC:

241

AN:

25792

East Asian (EAS)

AF:

0.00265

AC:

104

AN:

39176

South Asian (SAS)

AF:

0.00930

AC:

776

AN:

83448

European-Finnish (FIN)

AF:

0.0600

AC:

3175

AN:

52890

Middle Eastern (MID)

AF:

0.00493

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.0777

AC:

84976

AN:

1093064

Other (OTH)

AF:

0.0536

AC:

3176

AN:

59270

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

3934

7867

11801

15734

19668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0457

AC:

6966

AN:

152282

Hom.:

219

Cov.:

AF XY:

0.0435

AC XY:

3239

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0135

AC:

563

AN:

41554

American (AMR)

AF:

0.0381

AC:

583

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00806

AC:

AN:

3472

East Asian (EAS)

AF:

0.00173

AC:

AN:

5190

South Asian (SAS)

AF:

0.00726

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0586

AC:

622

AN:

10622

Middle Eastern (MID)

AF:

0.0205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0719

AC:

4893

AN:

68012

Other (OTH)

AF:

0.0517

AC:

109

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

360

721

1081

1442

1802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0610

Hom.:

662

Bravo

AF:

0.0435

Asia WGS

AF:

0.00751

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

1.3

(source)

DANN

Benign

0.53

PhyloP100

0.39

Mutation Taster

=295/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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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rs3761788

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over