chr6-24415152-G-A

Variant names:

• chr6-24415152-G-A
• rs3761788
• NM_020662.4:c.708G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.388
• Publications: 12 publications found

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]

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020662.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRS2	NM_020662.4	MANE Select	c.708G>A	p.Gln236Gln	synonymous	Exon 6 of 11	NP_065713.1
	MRS2	NM_001286264.2		c.717G>A	p.Gln239Gln	synonymous	Exon 7 of 12	NP_001273193.1
	MRS2	NM_001286265.2		c.708G>A	p.Gln236Gln	synonymous	Exon 6 of 10	NP_001273194.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRS2	ENST00000378386.8	TSL:1 MANE Select	c.708G>A	p.Gln236Gln	synonymous	Exon 6 of 11	ENSP00000367637.3
	MRS2	ENST00000378353.5	TSL:1	c.708G>A	p.Gln236Gln	synonymous	Exon 6 of 10	ENSP00000367604.1
	MRS2	ENST00000443868.6	TSL:2	c.717G>A	p.Gln239Gln	synonymous	Exon 7 of 12	ENSP00000399585.2

Frequencies

GnomAD3 genomes AF: 0.0458 AC: 6968 AN: 152166 Hom.: 219 Cov.: 32

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

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.: 30 AF XY: 0.0638 AC XY: 45335 AN XY: 710952

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: 28 AN: 5674

European-Non Finnish (NFE) AF: 0.0777 AC: 84976 AN: 1093064

Other (OTH) AF: 0.0536 AC: 3176 AN: 59270

GnomAD4 genome AF: 0.0457 AC: 6966 AN: 152282 Hom.: 219 Cov.: 32 AF XY: 0.0435 AC XY: 3239 AN XY: 74464

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: 28 AN: 3472

East Asian (EAS) AF: 0.00173 AC: 9 AN: 5190

South Asian (SAS) AF: 0.00726 AC: 35 AN: 4822

European-Finnish (FIN) AF: 0.0586 AC: 622 AN: 10622

Middle Eastern (MID) AF: 0.0205 AC: 6 AN: 292

European-Non Finnish (NFE) AF: 0.0719 AC: 4893 AN: 68012

Other (OTH) AF: 0.0517 AC: 109 AN: 2110

Alfa AF: 0.0610 Hom.: 662

Bravo AF: 0.0435

Asia WGS AF: 0.00751 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		0.39
Mutation Taster		=295/5	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3761788; hg19: chr6-24415380; COSMIC: COSV51234145;