rs2793422

Positions:

• chr6-24418120-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_020662.4(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 NM_020662.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.02

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MRS2	NM_020662.4	c.873G>A	p.Glu291Glu	synonymous_variant	8/11	ENST00000378386.8	NP_065713.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MRS2	ENST00000378386.8	c.873G>A	p.Glu291Glu	synonymous_variant	8/11	1	NM_020662.4	ENSP00000367637.3

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

GnomAD3 exomes AF: 0.317 AC: 79494 AN: 250874 Hom.: 13835 AF XY: 0.329 AC XY: 44538 AN XY: 135574

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 SAS exome AF: 0.287

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

Gnomad4 AFR exome AF: 0.121

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.212

Gnomad4 SAS exome AF: 0.292

Gnomad4 FIN exome AF: 0.319

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.338

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

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.274

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.217

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.378

Gnomad4 OTH AF: 0.301

Alfa AF: 0.366 Hom.: 17726

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	7.7
DANN	Benign	0.47

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

Other links and lift over

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