rs2793422

Variant names:

• chr6-24418120-G-A
• rs2793422
• NM_020662.4:c.873G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000378386.8(MRS2):​c.873G>A​(p.Glu291Glu) variant causes a synonymous change. The variant allele was found at a frequency of 0.342 in 1,612,414 control chromosomes in the GnomAD database, including 99,023 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 0.29 (7303 hom., cov: 31)
  • Exomes 𝑓: 0.35 (91720 hom.)
• Consequence: MRS2 ENST00000378386.8 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02
• Publications: 20 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.146).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378386.8. 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.873G>A	p.Glu291Glu	synonymous	Exon 8 of 11	NP_065713.1
	MRS2	NM_001286264.2		c.882G>A	p.Glu294Glu	synonymous	Exon 9 of 12	NP_001273193.1
	MRS2	NM_001286265.2		c.873G>A	p.Glu291Glu	synonymous	Exon 8 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.873G>A	p.Glu291Glu	synonymous	Exon 8 of 11	ENSP00000367637.3
	MRS2	ENST00000378353.5	TSL:1	c.873G>A	p.Glu291Glu	synonymous	Exon 8 of 10	ENSP00000367604.1
	MRS2	ENST00000443868.6	TSL:2	c.882G>A	p.Glu294Glu	synonymous	Exon 9 of 12	ENSP00000399585.2

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43758 AN: 151942 Hom.: 7314 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.218

Gnomad SAS AF: 0.284

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.304

GnomAD2 exomes AF: 0.317 AC: 79494 AN: 250874 AF XY: 0.329

Gnomad AFR exome AF: 0.122

Gnomad AMR exome AF: 0.211

Gnomad ASJ exome AF: 0.508

Gnomad EAS exome AF: 0.225

Gnomad FIN exome AF: 0.318

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.358

GnomAD4 exome AF: 0.348 AC: 508029 AN: 1460354 Hom.: 91720 Cov.: 34 AF XY: 0.350 AC XY: 254172 AN XY: 726528

African (AFR) AF: 0.121 AC: 4047 AN: 33424

American (AMR) AF: 0.220 AC: 9804 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.508 AC: 13265 AN: 26114

East Asian (EAS) AF: 0.212 AC: 8430 AN: 39686

South Asian (SAS) AF: 0.292 AC: 25150 AN: 86056

European-Finnish (FIN) AF: 0.319 AC: 17055 AN: 53408

Middle Eastern (MID) AF: 0.396 AC: 2278 AN: 5748

European-Non Finnish (NFE) AF: 0.367 AC: 407593 AN: 1110994

Other (OTH) AF: 0.338 AC: 20407 AN: 60316

GnomAD4 genome AF: 0.288 AC: 43727 AN: 152060 Hom.: 7303 Cov.: 31 AF XY: 0.287 AC XY: 21300 AN XY: 74310

African (AFR) AF: 0.128 AC: 5320 AN: 41518

American (AMR) AF: 0.274 AC: 4186 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1781 AN: 3468

East Asian (EAS) AF: 0.217 AC: 1122 AN: 5160

South Asian (SAS) AF: 0.285 AC: 1368 AN: 4808

European-Finnish (FIN) AF: 0.319 AC: 3358 AN: 10536

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25666 AN: 67980

Other (OTH) AF: 0.301 AC: 632 AN: 2102

Alfa AF: 0.356 Hom.: 22299

Bravo AF: 0.276

Asia WGS AF: 0.213 AC: 744 AN: 3478

EpiCase AF: 0.398

EpiControl AF: 0.402

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	7.7
DANN	Benign	0.47
PhyloP100		5.0
Mutation Taster		=236/64	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2793422; hg19: chr6-24418348; COSMIC: COSV51234332;